Plumbagin exerts antiobesity effects through inhibition of pancreatic lipase and adipocyte differentiation.

Plumbagin is a naphthoquinone found in the roots of Plumbago zeylanica. Here, we report an investigation to evaluate its antiobesity activity. The preliminary binding affinity of plumbagin to human pancreatic lipase (PL) was determined using molecular docking simulation. The in vitro PL inhibitory potential and the kinetics of inhibition were studied to validate and confirm the results obtained from molecular docking. The IC50 for PL was found to be 82.08 ± 9.47 µM, and the kinetics of inhibition was found to be of the mixed type. Further, the in vivo evaluation revealed that rats treated with plumbagin 1 mg/kg showed significant decrease in serum triglycerides (TG) and area under the curve of serum TG when compared with vehicle-treated rats. It was also seen that plumbagin possessed significant antiadipogenic effect as demonstrated by reduced oil red O staining and decreased TG contents. Thus, we conclude that plumbagin is a promising molecule to combat obesity and further optimization of plumbagin to yield plumbagin analogues will result in its improved activity profile.

Uteruslike masses of the ovary associated with breast cancer and raised serum CA 125.

We describe three cases of a uteruslike mass of the ovary, a condition in which the ovary is replaced by a mass that grossly and microscopically resembles the uterus. The patients were 38, 43, and 39 years of age, and only the first was nulliparous. Two of them also had breast carcinomas. Two patients also had elevated CA 125 levels that gave rise to a clinical suspicion of ovarian malignancy. There were no anatomic abnormalities in any of the patients. The presence of residual ovarian stroma in two of the patients (both of whom had breast cancer) suggests that metaplasia rather than a congenital anomaly is the cause. Elevated CA 125 levels are consistent with the endomyometriosis nature of the lesion.

Teratocarcinosarcoma of the paranasal sinuses: a clinicopathologic and immunohistochemical study.

We report four cases of sinonasal teratocarcinosarcoma (SNTCS), a rare malignant tumor that displays combined features of an immature or malignant teratoma and a carcinosarcoma. The patients, three men and one woman, were all adults ranging in age from 21 to 69 years who presented with nasal obstruction and epistaxis. The tumors were typically composed of round cells and short spindle cells with neuroectodermal/rosette-like structures. Also seen were foci of fetal-like squamous epithelium, glandular epithelium, immature mesenchyme, immature cartilage, and neuronal differentiation. Immunohistochemistry performed in three cases showed expression of vimentin, CD99 (MIC2), and neuron-specific enolase in most cells, and focal expression of cytokeratin, epithelial membrane antigen, alpha fetoprotein, glial fibrillary acidic protein, chromogranin, and synaptophysin. The tumors were consistently negative for beta human chorionic gonadotrophin, neurofilament protein, and leukocyte common antigen. The entities considered in the differential diagnosis were poorly differentiated carcinomas, sarcomas, and olfactory neuroblastoma. We suggest that these neoplasms arise from a primitive cell capable of organized divergent differentiation.

Can genetic instability be studied at the single chromosome level in cancer cells? Evidence from human melanoma cells.

We evaluated whether genetic instability, which is the hallmark of cancer cells, can be investigated at the single chromosomal level. We established in culture and examined a human malignant melanoma cell line and its 11 distinct clones as well as peripheral blood cultures from the original patient by G-banding, C-banding, and silver-staining (AgNOR) techniques. There were six marker chromosomes common to most of the 11 clones and eight or nine additional marker chromosomes found in only one or in very few clones. Chromosome 1 had a pericentric inversion in the C-banded region in both the tumor and the lymphocyte metaphase spreads. This same homologue was also involved in the formation of one of the shared marker chromosomes; this marker, in turn, was rearranged to form two unique markers in one clone. Our findings suggest that genetic instability can be studied at the single chromosome level. Moreover, this study further supports our earlier contention that peripheral blood lymphocyte cultures can show chromosomal lesions that are stable markers in cancer cells.

Reduced DNA repair capacity in breast cancer patients and unaffected individuals from breast cancer families.

It has been suggested that increased fragile site expression in lymphocyte cultures can be used as a marker for genetic predisposition to cancer. We wished to determine whether aphidicolin (APC), an inhibitor of the DNA repair enzyme DNA polymerase alpha, could be used as a reliable biomarker in identification of DNA repair capacity in unaffected individuals at high risk from breast cancer families. PHA-stimulated lymphocyte cultures, with and without APC, were set up in 65 individuals, of whom 14 were breast cancer patients, 26 were unaffected individuals from breast cancer families, and 25 were controls. A significant proportion of breast cancer patients and unaffected individuals from familial breast cancer (FBC) families exhibited premature separation of centromeres (PSC) and aneuploidy in the untreated cultures. In the APC treated cultures, almost all such individuals exhibited a marked depression of mitotic index and increased aneuploidy, as compared to controls. Our results indicate that these individuals have defective DNA repair capacity. Such individuals could thus have a much higher risk of cancer as compared to persons exhibiting PSC and aneuploidy or DNA repair defects alone. We propose that APC may be a valuable biomarker in identifying individuals with genetic predisposition to cancer from FBC families.

Filtration and agar embedding applied to fine needle aspirates for tumor diagnosis by electron microscopy. A combined technique.

OBJECTIVE: To develop a novel method for processing of fine needle aspirates subjected to electron microscopic (EM) study. STUDY DESIGN: Included 70 cases of poorly differentiated malignant tumors in which a definitive diagnosis was not possible on light microscopic (LM) examination and that thus required application of an ancillary technique such as FNA/EM, for diagnosis. We have established a novel method of processing, a technique of filtration through nylon mesh filters to eliminate red blood cells (RBCs) and necrotic debris, followed by agar well embedding to avoid loss of diagnostic material during processing without centrifugation at later steps after agar embedding, thus minimizing the time required for processing. It was successfully carried out in 70 cases. RESULTS: The combined technique was extremely effective in eliminating RBCs and necrotic debris. It also avoided further loss of valuable diagnostic material. An accurate diagnosis was rendered in 70 cases; that was not possible by LM alone. The whole procedure saves two to three hours of processing as centrifugation is not required after the agar embedding step. CONCLUSION: This technique was found to be cost- and time-effective, particularly suitable for developing countries, where financial resources are limited.

Psammomatous carcinoid tumor of the duodenum.

We report a case of psammomatous calcification in a carcinoid tumor of the ampulla of Vater. Although the tumor was glandular, its neuroendocrine nature was proved using chromogranin immunostain.

Collision tumor with three components at esophagogastric junction.

We report a 70-year-old man with a collision tumor consisting of three neoplasms at the gastroesophageal junction. The component tumors were squamous carcinoma at the esophageal and, adenocarcinoma at the gastric end, and leiomyoma within.

Pseudolymphomatous phase of Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto lymphadenitis is a distinctive entity which is easily recognised in its classical histology. However, cases which are biopsied in the early stage of the disease, before entering the necrotic phase may be misdiagnosed as non-Hodgkin's lymphoma. Ten cases of Kikuchi-Fujimoto disease which mimicked non-Hodgkin's lymphoma and in which less than 10% of the lymph node was occupied by necrosis were chosen for this study. The patients included 4 males and 6 females with an age range of 15-40 years. Eight patients presented with cervical lymphadenopathy. The pathologic areas ranged from 70% to 95% of the total nodal area. The features that helped distinguish this lesion from non-Hodgkin's lymphoma were: 1) a sprinkling of karyorrhectic debris throughout the node 2) plasmacytoid monocytes as well as "histiocytes" in the company of transformed lymphocytes (immunoblasts) 3) enlarged mottled T-zone areas, and 4) presence of residual lymphoid follicles. Follow up on six patients revealed no evidence of disease.

Rhabdoid phenotype in squamous carcinoma. A report of two cases.

We report two cases of squamous carcinoma in which a prominent rhabdoid phenotype was seen. The tumors which occurred in the buccal mucosa of a 70 year old man and the skin of a 85 year old man were positive for cytokeratin and epithelial membrane antigen indicating their epithelial nature. Co-expression of vimentin was also noted. The aggressive nature of the rhabdoid component is confirmed by the fact that the cervical lymph node metastasis in case I was also rhabdoid.

Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice.

Cancer cells from five oral cancer patients and pleomorphic adenoma cells from one individual were inoculated as single cell suspension into subcutis of 30 Swiss nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from three oral cancer patients were xenografted s.c. in 18 nude mice, and 10 mice were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice, developed squamous cell carcinoma at the site of inoculation within 8-15 days, while tumors were not observed in mice inoculated with single cell suspension, up to 60/90 days. In 8/68 (12%) mice, white foci were observed in several tissues, with hepatomegaly and splenomegaly noted in 27/68 (39%) mice. Histopathological examination of various tissues revealed presence of large cell lymphoma in several organs in 14/68 (21%) mice. No regional or distant metastasis of the implanted oral tumor cells was detected. Mice injected with cells from pleomorphic adenoma, also demonstrated large cell lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%) lymphomas exhibited positive reaction with mouse B cell antibodies illustrating the murine origin of the lymphomas, and these were immunophenotyed as B cell lymphomas. The lymphomas were also examined with mouse T cell antibodies and none reacted positively with the mouse T cell antibodies. The lymphomas also failed to react with human T cell, B cell and human Leucocyte common antigen (LCA) antibodies, indicating that the induced lymphomas were not of human origin. The tumor specimens from seven of eight oral cancer patients and the pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that xenografting oral tumor cells into nude mice may cause induction of the murine lymphomas, and this needs further investigation.

Heterotopic ossification in colorectal adenocarcinoma [corrected].

Heterotopic ossification in Adenocarcinomas of the colon is uncommon. The clinical presentation of these patients is similar to those without osseous metaplasia. Its importance lies in the fact that it may be misdiagnosed for a carcinosarcoma. Which has a poorer prognosis. These two cases are reported because of its rarity.

Potential of ozonated sesame oil to augment wound healing in rats.

The hypothesis that ozonated oil has wound healing property was investigated in an excision wound model using Sprague Dawley rats. The animals were divided into four groups, which were treated with sesame oil (vehicle), framycetin (standard), or two doses of ozonated sesame oil (peroxide values 500 and 700 mEq/1000 g, respectively). The formulations were topically applied on the excision wounds once daily for 11 consecutive days and the animals were euthanized on the 12(th) day. Wound healing was assessed by measuring the wound contracture, tensile strength, collagen content and superoxide dismutase activity of skin of the excised wound area. On the terminal day, areas of the wounds of the group receiving high dose ozonated oil were significantly smaller than those of the group treated with vehicle. Ozonated oil treated wounds had significantly higher tensile strength, collagen content and superoxide dismutase activity than that of the vehicle treated wounds. Histopathological analysis of skin of the excised wound area treated with ozonated oil revealed better healing activity vis-à-vis vehicle-treated wounds. Thus, it can be concluded that ozonated oil can be of potential therapeutic use for healing wounds.