Multifaceted role of phytoconstituents based nano drug delivery systems in combating TNBC: A paradigm shift from chemical to natural.

Triple negative breast cancer is considered to be a malignancy of grave concern with limited routes of treatment due to the absence of specific breast cancer markers and ambiguity of other potential drug targets. Poor prognosis and inadequate survival rates have prompted further research into the understanding of the molecular pathophysiology and targeting of the disease. To overcome the recurrence and resistance mechanisms of the TNBC cells, various approaches have been devised, and are being continuously evaluated to enhance their efficacy and safety. Chemo-Adjuvant therapy is one such treatment modality being employed to improve the efficiency of standard chemotherapy. Combining chemo-adjuvant therapy with other upcoming approaches of cancer therapeutics such as phytoconstituents and nanotechnology has yielded promising results in the direction of improving the prognosis of TNBC. Numerous nanoformulations have been proven to substantially enhance the specificity and cellular uptake of drugs by cancer cells, thus reducing the possibility of unintended systemic side effects within cancer patients. While phytoconstituents offer a wide variety of beneficial active constituents useful in cancer therapeutics, most favorable outcomes have been observed within the scope of polyphenols, isoquinoline alkaloids and isothiocyanates. With an enhanced understanding of the molecular mechanisms of TNBC and the advent of newer targeting technologies and novel phytochemicals of medicinal importance, a new era of cancer theranostic treatments can be explored. This review hopes to instantiate the current body of research regarding the role of certain phytoconstituents and their potential nanoformulations in targeting specific TNBC pathways for treatment and diagnostic purposes.

LINE-1 retrotransposon encoded ORF1p expression and promoter methylation in oral squamous cell carcinoma: a pilot study.

Oral squamous cell carcinoma (OSCC) is highly predominant in India due to excessive use of tobacco. Here we investigated Long INterpersed Element 1 (LINE or L1) retrotransposon activity in OSCC samples in the same population. There are almost 500,000 copies of L1 occupied around 30%  of the human genome. Although most of them are inactive, around 150-200 copies are actively jumping in a human genome. L1 encodes two proteins designated as ORF1p and ORF2p and expression of both proteins are critical for the process of retrotransposition. Here we have analyzed L1 ORF1p expression in a small cohort (n = 15) of paired cancer-normal tissues obtained from operated oral cancer patients. Immunohistochemistry (IHC) with the human ORF1 antibody showed the presence of ORF1p in almost 60%  cancer samples, and few of them also showed aberrant p53 expression.  Investigating L1 promoter methylation status, showed certain trends towards hypomethylation of the L1 promoter in cancer tissues compared to its normal counterpart. Our data raise the possibility that L1ORF1p expression might have some role in the onset and progression of this particular type of cancer.

Evaluation of Iron Status in Patients of Chronic Kidney Disease - A Study to Assess the Best Indicators Including Serum Transferrin Receptor Assay.

Anemia is an early complication of chronic kidney disease (CKD). The iron deficiency is an important contributor, more so in the Indian population. As routine standalone iron tests do not accurately reflect the actual status in the complex environment of CKD, there is a need to study better indicators. Serum iron, ferritin, total iron-binding capacity (TIBC), and serum transferrin receptor (sTfR) levels were estimated in 100 primary iron deficiency anemia (IDA) patients (controls-Group 1) and 68 newly diagnosed CKD cases. The CKD patients were divided into two groups: Serum ferritin <=100 µg/L (Group 2) and >100 µg/L (Group 3). The values of percentage saturation, log of ferritin (log_ferritin), and the ratio of sTfR to log ferritin (sTfR/log_f or sTfR index) were calculated. The CKD cases were further divided depending on ferritin cut-offs of 30, 50, 70, and 100 µg/L and statistically analyzed including ROC and AUC, to choose the best diagnostic parameter for accurate assessment of iron status in CKD cases. The mean serum ferritin was 11.34 µg/L, 28.70 µg/L, and 281.81 µg/L, and the mean sTfR was 2.34 µg/ml, 1.82 µg/ml, and 1.28 µg/ml in Groups 1, 2, and 3. Among all groups, the difference was found to be significant for serum iron, log_ferritin, and sTfR/log_f. The sTfR and sTfR/log_f showed good discrimination between IDA and Anemia of chronic disease in CKD cases, but sTfR/log_f gave the best discrimination at all cut-off levels of ferritin. At a ferritin cut-off of 50 µg/L, the sTfR/log_f value of 0.83 had a sensitivity of 93.5% and specificity of 95.45%, and at a ferritin cut-off 100 µg/L, the same value of 0.83 had a sensitivity of 95.5% and specificity of 86.5%. The ratio of sTfR/log_f is the best indicator for assessing iron status in CKD.

A study of BRAF mutation in colorectal carcinoma in Indian population.

CONTEXT: BRAF mutation has been extensively studied and associated with various tumors. Targeted therapeutic intervention against BRAF mutation is established modality against many such tumors. Various studies have estimated that the prevalence of BRAF mutation in colorectal carcinoma (CRC) is 5%-25%. Considering epidemiology differences from Western population and paucity of studies on BRAF mutation in CRC in Asian patients, the present study was done to study the BRAF mutation in CRC in Indian population. AIMS: The aim is to study the distribution of BRAF mutation and its correlation with the American Joint Committee on Cancer (AJCC) stage, grade, and other clinicopathological parameters in CRC. SETTINGS AND DESIGN: This was a cross-sectional study. SUBJECTS AND METHODS: Immunohistochemistry study was done using BRAFV600E monoclonal antibody (Clone VE1) for 65 consecutive cases of CRC in a tertiary care center. The results were statistically analyzed using SPSS version 2.0. RESULTS: This study found that BRAF mutation is not significantly present in CRC as only 4.6% of cases were positive for BRAFV600E mutation. However, there was statistically significant relation between increasing AJCC stage and BRAF mutation. CONCLUSIONS: This study concluded that BRAF mutation is not prevalent in Indian population with CRC. However, it is significantly related with advanced AJCC stages.

Greater auricular nerve masquerading as lymph node.

Hansen's disease is on the verge of being eliminated from India and often missed by clinicians due to low index of suspicion. We present an unusual case in which greater auricular nerve thickening masqueraded as enlarged lymph node in the neck. The patient was referred for fine needle aspiration cytology, which revealed epithelioid cell granulomas suggestive of Hansen's disease. Further clinical examination and investigations including the skin biopsy confirmed the disease, highlighting the role of pathologist in the management of such unusual presentation of a common disease.

Role of anion gap and different electrolytes in hypertension during pregnancy (preeclampsia).

The present study was designed to determine the changes in serum sodium, anion gap, different antioxidants and free radicals in preeclamptic patients and control subjects. Serum sodium, chloride, bicarbonate, calcium, potassium and magnesium were estimated and anion gap was determined in 100 proteinuric hypertensive and 100 normotensive pregnant women. Mean serum sodium, chloride and bicarbonate level (133.26 +/- 13.1, 104.97 +/- 11.37, and 22.01 +/- 4.66 mEq/l, respectively) were significantly higher in proteinuric hypertensive women as compared to controls (125.85 +/- 10.4, 101.90 +/- 6.3, 19.34 +/- 3.21 mEq/l, respectively) whereas anion gap level (6.28 +/- 16.147) was nonsignificantly higher in proteinuric hypertensive as compared to normotensive (4.61 +/- 11.84). Total serum sodium concentration increases in preeclamptic subjects, the exact distribution of serum sodium in various compartments of the body are not clear and correlation of serum sodium and anion gap with proteinuria is also not known. The levels of different antioxidants were decreased in preeclamptic patients as compared to the controls while the level of free radicals elevated in preeclamptic subjects as compared to controls. In our study, anion gap level was found to be rather non-significantly higher in proteinuric hypertensive women as compared to normotensive women.

Maternal and perinatal outcome in idiopathic thrombocytopenic purpura (ITP) with pregnancy.

BACKGROUND: Idiopathic thrombocytopenic purpura commonly affects women of childbearing age and is associated with maternal and fetal complications. Management of a pregnant patient is difficult and requires combined care of obstetrician and a neonatologist. We report our experience of idiopathic thrombocytopenic purpura during pregnancy during the last 7 years. METHOD: A retrospective study over the 7-year period 1997-2003 was carried out in the Department of Obstetrics and Gynaecology in the Postgraduate Institute of Medical Education and Research, Chandigarh, India. The course of pregnancy, disease and perinatal outcome of 19 pregnancies in 16 patients with idiopathic thrombocytopenic purpura was studied. RESULTS: Out of 16 patients with idiopathic thrombocytopenic purpura, eight were already diagnosed while the other eight were diagnosed during pregnancy. Five patients diagnosed during pregnancy had severe thrombocytopenia, and four of them showed hemorrhagic manifestation. Nine patients required steroids during pregnancy. Two patients received immunoglobulin therapy. During the antenatal period one patient developed pre-eclampsia and one patient had gestational diabetes mellitus. Both of these patients were on steroids. There was no postpartum hemorrhage or maternal death. None of the neonates had bleeding complication, irrespective of mode of delivery. CONCLUSION: Pregnant patients with idiopathic thrombocytopenic purpura have generally good maternal and perinatal outcomes.

Aqua mediated synthesis of substituted 2-amino-4H-chromenes and in vitro study as antibacterial agents.

A simple, clean, environmentally benign route to the synthesis of 2-amino-chromenes is described using K2CO3 as a green catalyst in water under microwave irradiation. This implies a convenient route avoiding the usage of hazardous organic solvents and organic bases. This technique requires only water in both the reaction step and workup, thus rendering the whole procedure into a truly ecofriendly green protocol. All the synthesized compounds were shown to possess antibacterial activity as tested in vitro against standard strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.