The incidence and mortality of cervical cancer remains high in India even after sixty years of introduction of the Pap smear (cervical cytology) which is an effective means of identifying preinvasive lesions of carcinoma cervix. The morbidity and mortality due to cervical cancer has come down drastically in countries with well established screening programmes at national level. This study aims at screening women for cervical cancer opportunistically during their visit to hospital and to study various types of neoplastic and non-neoplastic lesions of the cervix by cervical smear study (Pap smear study). In the present study, a total of 350 cervical smears were studied. The age of patients ranged from 19 years to 80 years with mean age being 37.5 years. Out of 350 cases, the diagnosis of neoplasia was given in 43 cases and 258 cases were diagnosed as inflammatory smears. Forty-cases were normal and 9 cases were inadequate to evaluate. Forty-three patients who were found to have neoplastic lesions on cytology were referred for further investigations like colposcopy and biopsy to confirm the diagnosis and avail proper treatment. Limitation of the present study was small sample size as all female patients aged between 20 and 60 years visiting hospital were not included in the screening, other screening tests like VIA (visual inspection with acetic acid test) and HPV DNA (human papilloma virus) tests were not done. Until the time centrally organised screening programmes for cervical cancer are established in India, arrangements should be made for hospital based opportunistic screening for all women attending hospital. The cost effectiveness of different screening tests for cervical cancer should be evaluated.

Histone deacetylases (HDACs), which modulate the expression of genes, are potential therapeutic targets in several cancers. Targeted inhibition of HDAC prevents the expression of oncogenes thereby help in the treatment of cancers. Hence, several pharmaceutical companies developed inhibitors of HDAC and tested them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic acid) is one such HDAC inhibitor developed for treating breast and colorectal carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA for treating cancers was discouraged. Similarly another HDAC inhibitor Trichostatin-A (TSA) also showed promising results in clinical trials but exhibited severe adverse effects, which dampened the interest of using this molecule for cancer treatment. Therefore, search for developing a potent HDAC inhibitor with minimal side effects still continues. Hence, in this study we have screened benzoic acid and benzoic acid derivatives with hydroxylic (-OH) groups and methoxy (-OCH3) groups for their efficacy to bind to the TSA binding site of HDAC using molecular docking studies. Molecules that showed much stronger affinity (than TSA) to HDAC were tested for inhibiting HDAC expressing cultured cancer cells. DHBA but not Dimethoxy Benzoic Acid (DMBA) inhibited HDAC activity, leading to cancer cell growth inhibition through the induction of ROS and cellular apoptosis mediated by Caspase-3. In addition, DHBA arrested cells in G2/M phase of the cell cycle and elevated the levels of sub-G0-G1 cell population. In summary, results of this study report that DHBA could be a strong HDAC inhibitor and inhibit cancer cell growth more effectively.

Recent studies from our group and many others have shown the ability of histone deacetylase (HDAC) inhibitors for retarding the growth of carcinomas of cervix, colon and rectum in vitro. A search for naturally occurring HDAC inhibitors continues due to the adverse effects associated with known HDAC inhibitors like SAHA and TSA. Therefore in the current study, naturally occurring cinnamic acids derivatives were screened for HDAC inhibitory effect using in silico docking method which identified cinnamic acids as potential candidates. Cinnamic acids (CA) are naturally occurring phenolic compounds known to exhibit anticancer properties. However, it is not clearly known whether the anticancer properties of CA derivatives are due to the inhibition of oncogenic HDACs, if so how the efficacy varies among various CA derivatives. Hence, the HDAC inhibitory potential of CA derivatives containing increasing number of hydroxylic groups or methoxy moieties was determined using Discovery Studio software and the most potent CA derivatives tested ex vivo (biochemical assay) as well as in vitro (using cell based assay). Among CA derivatives tested, dihydroxy cinnamic acid (DHCA, commonly known as caffeic acid) exhibited better interactions with HDAC2 (compared to other isoforms) in silico and inhibited its activity ex vivo as well as in vitro. Targeted reduction of HDAC activity using DHCA induced death of cancer cells by (a) generating reactive oxygen species, (b) arresting cells in S and G2/M phases; and (c) induction of caspase-3 mediated apoptosis. In conclusion, we demonstrated that DHCA inhibited cancer cell growth by binding to HDAC followed by the induction of apoptosis.

Neuromuscular and vascular hamartoma (NMVH) is a rare lesion arising chiefly in the small intestine. As it shares many of the histological features with other commonly occurring stricturous conditions of the small bowel, there is an ongoing debate whether it is truly hamartomatous or represents just a reactive condition. We are reporting a case of NMVH in the terminal ileum in a 32-year-old male who presented with symptoms of intestinal obstruction.

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