Synthesis of 2-phenyl-4,5-substituted oxazoles by copper-catalyzed intramolecular cyclization of functionalized enamides.

An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel ß-(methylthio)enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis-decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU-mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of ß-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.

Management of gingivobuccal complex cancer.

INTRODUCTION: Squamous cell carcinoma of the oral cavity ranks as the 12th most common cancer in the world and the 8th most frequent in males. It accounts for up to one-third of all tobacco-related cancers in India. Cancer of the gingivobuccal complex is especially common in Indians due to their tobacco habits. This review focuses on the management of lower gingivobuccal complex cancers. PATIENTS AND METHODS: References for this review were identified by search of Medline and other bibliographic information available in the PubMed database. The search terms carcinoma oral cavity, and cancer oral cavity, buccal mucosa, gingiva, gingivobuccal complex, and alveolus cancer/carcinoma were used. References from relevant articles and abstracts from international conferences were also included. Only articles published in the English language were used. RESULTS: Treatment of gingivobuccal complex cancer is primarily surgical. Radical neck dissection, or its modification, is the standard treatment for the node-positive neck. Supraomohyoid neck dissection is the accepted treatment for the node-negative neck. Radiotherapy is usually not the preferred modality of treatment for early gingivobuccal complex cancer. It is used either as postoperative adjuvant treatment or as definitive treatment for advanced cancer with or without chemotherapy. Chemotherapy has been used as neo-adjuvant, adjuvant or palliative treatment. Advanced cancers are common and continue to pose a challenge to the multidisciplinary team. CONCLUSIONS: Gingivobuccal complex cancer remains a major public health problem despite being highly preventable and easily detectable. Advanced cancers constitute a major proportion of patients presenting for treatment. These patients are difficult to treat and have a poor outcome.

An efficient highly regioselective synthesis of 2,3,4-trisubstituted pyrroles by cycloaddition of polarized ketene S,S- and N,S-acetals with activated methylene isocyanides.

An efficient route for regioselective synthesis of 2,3,4- substituted pyrroles allowing precise control over the introduction of a number of substituents and functionalities (tosyl, carbalkoxy, aryl, cyano, nitro, acetyl, benzoyl, cyclic amines, etc.) at the three positions of the pyrrole ring has been developed via 1,3-dipolar cycloaddition of readily accessible polarized ketene S,S- and N,S-acetals with carbanions derived from activated methylene isocyanides.

Gallbladder cancer.

Gallbladder cancer (GBC) is the most common malignancy of the biliary tract and the fifth most common gastrointestinal (GI) cancer. In addition to global inter-country variations in incidence, large racial and ethnic variations have been noted within countries. High incidence rates of GBC have been described in North India, for example. Despite the fact that the precise etiology of GBC is poorly understood, a strong association between GBC and cholelithiasis exists. Most GBC presents clinically as advanced disease with unfavorable prognosis and poor response to treatment. A small but increasing proportion of cases of incidental GBC detected during or after cholecystectomy is also being seen. Such patients are generally in an earlier stage of disease and are potentially more curable by a completion radical cholecystectomy, which is especially indicated for patients whose disease is stage pT1b or beyond. Radical surgery is the mainstay of curative intent treatment for GBC. When feasible, extended or radical cholecystectomy is the standard treatment for resectable GBC. Patients with advanced stage III or IV disease may undergo more complex, high-risk, and morbid extended resections such as hepatopancreaticoduodenectomy. We believe that these procedures should be performed only in selected patients at centers specializing in these resections. Patients not fit for such major resection or found unresectable on imaging or exploration are usually offered palliative treatment. This may be in the form of surgical palliation (eg, palliative bypass for gastric outlet, bowel, or biliary tract obstruction), endoscopic biliary stenting (for obstructive jaundice), or palliative chemotherapy. Chemotherapy for GBC is generally used in the palliative setting. Gemcitabine, cisplatin, 5-fluorouracil, mitomycin, and capecitabine are some of the effective agents. We have reported gratifying overall response rates of 55% with the combination of gemcitabine and cisplatin in patients with advanced GBC. Patients with advanced GBC and jaundice who undergo stenting followed by chemotherapy show response and survival rates similar to those who present without jaundice.

Overexpression of p53 protein in gallbladder carcinoma in North India.

AIMS: p53 mutations are one of the most frequent genetic alterations in human cancers and are thought to play a role in pathogenesis of several malignancies. Overexpression of p53 in gallbladder cancer has not previously been reported from North India which has one of the highest incidence of this malignancy in the world. The present work is aimed at studying the overexpression of p53 in gallbladder carcinoma occurring in North India. METHODS: p53 overexpression by immunohistochemistry was studied in 20 operative specimens of gallbladder carcinoma. The clinico-pathological observations of these patients were correlated with the extent of p53 overexpression. RESULTS: Seventy per cent (14/20) of specimens of gallbladder carcinoma overexpressed p53 protein. There was a significant correlation between presence of gallstones, T stage, grade of tumour and liver invasion with p53 overexpression. There was no significant correlation with other factors studied viz. age, sex, nodal status and histological type. CONCLUSIONS: The results show a strong association between gallstones and p53 protein overexpression in gallbladder carcinoma. The causal relationship in this association, however, still remains unproven.

Bladder teratoma: a case report and review of literature.

A very rare case of Teratoma of the bladder in an eight year old girl is presented. The diagnosis was made on cyctoscopy and confirmed histopathologically. Complete excision was possible. No recurrence was seen at four years follow up. Only one such case has been reported in the literature and this is the first such case reported from India and Asian continent.

Phytobezoar extending from stomach to cecum.

We report a patient with a phytobezoar extending from the stomach through the small intestine to the cecum. The patient presented with acute intestinal obstruction and bezoar was suspected at exploration. The specimen showed two masses of cotton fibres connected with a long string of variable thickness.

Centchroman--a non-steroidal anti-cancer agent for advanced breast cancer: phase-II study.

Treatment with Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) phenyl-7-methoxy chroman) has been evaluated in 4 male and 75 female patients with advanced breast cancer. The overall response rate, including both male and female cases, was 40.5%. Among the female patients, the overall response rate was 38.7%. The median duration of response was 6 months. One of the 4 male patients showed a complete response and 2 showed partial responses. The responses were more marked for bone, pulmonary, soft tissue, skin and lymph-node metastases than for liver metastases.

Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma.

Improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kg on day 1,5-FU in a dose of 8-10 mg/kg on days 2-5, and MMC on day 6. This schedule was reinitiated on days 8 and 15 for total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT), and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of 8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects.

Inhibition by 4'-demethyl-epipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside) of human lymphoblast cultures in G2 phase of the cell cycle.

4'-Demethyl-epipodophyllotoxin 9-(4,6-0-2-thenylidene-beta-D-glucopyranoside) is a semisynthetic derivative of podophyllotoxin with oncolytic activity against a variety of neoplasms, Unlike the parent compound and other derivatives, which cause methaphase arrest, 4'-Demethyl-epipodophyllotoxin 9-(4,6-0-2-thenylidene-beta-D-glucopyranoside) apparently blocks the entry of CCRF-CEM cells into mitosis by inhibiting cells in the G2 phase of the cell cycle. The inhibition of precursor incorporation into DNA, RNA, and the protein, if observed, was delayed and probably secondary to inhibition of cells in the G2 phase of the cell cycle.