Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma.

Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples. We found promoter hypermethylation frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with hypermethylation were significantly lower. Multivariable analysis confirmed that LATS1 under expression increased the hazard of death after adjusting for other clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was associated with overall short survival. LATS1 is an independent prognostic factor and may play an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.

Atomic Insight into the Altered O6-Methylguanine-DNA Methyltransferase Protein Architecture in Gastric Cancer.

O6-methylguanine-DNA methyltransferase (MGMT) is one of the major DNA repair protein that counteracts the alkalyting agent-induced DNA damage by replacing O6-methylguanine (mutagenic lesion) back to guanine, eventually suppressing the mismatch errors and double strand crosslinks. Exonic alterations in the form of nucleotide polymorphism may result in altered protein structure that in turn can lead to the loss of function. In the present study, we focused on the population feared for high exposure to alkylating agents owing to their typical and specialized dietary habits. To this end, gastric cancer patients pooled out from the population were selected for the mutational screening of a specific error prone region of MGMT gene. We found that nearly 40% of the studied neoplastic samples harbored missense mutation at codon151 resulting into Serine to Isoleucine variation. This variation resulted in bringing about the structural disorder, subsequently ensuing into a major stoichiometric variance in recognition domain, substrate binding and selectivity loop of the active site of the MGMT protein, as observed under virtual microscope of molecular dynamics simulation (MDS). The atomic insight into MGMT protein by computational approach showed a significant change in the intra molecular hydrogen bond pattern, thus leading to the observed structural anomalies. To further examine the mutational implications on regulatory plugs of MGMT that holds the protein in a DNA-Binding position, a MDS based analysis was carried out on, all known physically interacting amino acids essentially clustered into groups based on their position and function. The results generated by physical-functional clustering of protein indicated that the identified mutation in the vicinity of the active site of MGMT protein causes the local and global destabilization of a protein by either eliminating the stabilizing salt bridges in cluster C3, C4, and C5 or by locally destabilizing the "protein stabilizing hing" mapped on C3-C4 cluster, preceding the active site.

Total leucocyte count, C-reactive protein and neutrophil count: diagnostic aid in acute appendicitis.

BACKGROUND/AIM: Acute appendicitis is one of the most common acute intraabdominal affections seen in surgical departments, which can be treated easily if an accurate diagnosis is made in time. Otherwise, delay in diagnosis and treatment can lead to diffuse peritonitis. MATERIALS AND METHODS: A study was conducted on 110 patients who were operated for acute appendicitis to determine the role and predictive value of the total leucocyte count (TLC), C-reactive protein (CRP) and percentage of neutrophil count in the diagnosis of acute appendicitis. Preoperative TLC, CRP and percentage of neutrophil count were determined and were compared with the results of the histopathology of the removed appendix. RESULTS: Of all the patients studied, 92 had histopathologically positive appendicitis. The TLC was found to be significantly high in 90 patients who proved to have acute appendicitis, whereas CRP was high in only 88 patients and neutrophil percentage was raised in 91; four had a normal CRP level. Thus, TLC had a sensitivity, specificity and positive predictive value of 97.82%, 55.55% and 91.8%, respectively. CRP had a sensitivity, specificity and positive predictive value of 95.6%, 77.77% and 95.6% respectively. Percentage of neutrophil count had a sensitivity, specificity and positive predictive value of 98.9%, 38.88% and 89.21%, respectively. When used in combination, there was a marked improvement in the specificity and the positive predictive value to 88.04% and 98.7%, respectively. CONCLUSION: The inflammatory markers, i.e., TLC, CRP and neutrophil count can be helpful in the diagnosis when measured together as this increases their specificity and positive predictive value.

Giant primary omental cyst mimicking a pseudoascites.

Primary omental cysts are rare intra-abdominal pathology, which are difficult to diagnose preoperatively; as such a high index of suspicion is required for accurate preoperative diagnosis. We present a case of primary omental cyst in an eight-year-old girl who presented with huge abdominal distension mimicking ascites. She was operated and cyst was extirpated completely. Histological examination revealed an omental cyst with endothelial lining and haemorrhagic fluid inside. Patient was followed up for a period of one year and had no post operative complication or recurrence of the disease. This case is reported to emphasise the inclusion of huge omental cyst in the differential diagnosis of ascites especially in the paediatric age group.

Abdominal pregnancy as a cause of hemoperitoneum.

The coexistence of intrauterine and extrauterine pregnancy, the heterotopic pregnancy, is a rare obstetric phenomenon. The preoperative diagnosis of this condition is very difficult; leading to a higher maternal morbidity and fetal loss. We experienced a case of intrauterine pregnancy and ruptured abdominal pregnancy implanted on the illeocaecal region in a 26-year-old primiparous woman. She was clinically misdiagnosed as a case of ruptured ectopic pregnancy, but ultrasonography showed it to be a case of heterotopic pregnancy. Subsequently, the patient was subjected to laparotomy and the ruptured abdominal pregnancy was evacuated. She continued with the intrauterine pregnancy till term and delivered a healthy female baby. Although this condition is unusual, any general surgeon in the emergency department must be aware of this complication and its management, which is often initially misdiagnosed.