Resveratrol, cancer and cancer stem cells: A review on past to future.

Cancer remains to be an unresolved medical challenge despite of tremendous advancement in basic science research and clinical medicine. One of the major limitations is due to the side effects of chemotherapy which remains to be palliative without offering any permanent cure for cancer. Cancer stem cells (CSCs) are the subpopulation of cells in tumors that remain viable even after surgery, chemo- and radio-therapy that eventually responsible for tumor relapse. Hence, by eliminating non-stem cancer cells and cancer stem cells from the patient, permanent cure is expected. Phytochemicals have been under the intensive study to target these CSCs effectively and permanently as they do not cause any side effects. Resveratrol (RSV) is one such compound attaining lot of interest in recent days to target CSCs either alone or in combination. RSV has been used by several researchers to target cancer cells in a variety of disease models, however its CSC targeting abilities are under intensive study at present. This review is to summarize the effects of RSV under in vitro and in vivo conditions along with advantages and disadvantages of its uses against cancer cells and cancer stem cells. From the first reports on phytochemical applications against cancer and cancer stem cells in 1997 and 2002 respectively followed by later reports, up to date observations and developments are enlisted from PubMed in this comprehensive review. RSV is shown to be a potential compound having impact on altering the signal transduction pathways in cancer cells. However, the effects are variable under in vitro and in vivo conditions, and also with its use alone or in combination with other small molecules. Past research on RSV is emphasizing the importance of in vivo experimental models and clinical trials with different prospective combinations, is a hope for future promising treatment regimen.

Aberrant signal transduction in Indian triple-negative breast cancer patients.

AIM OF STUDY: The aim of this study is to correlate the prominin-1 or CD133 association with functional pathway markers of cancer stemness in Indian triple-negative breast cancer (TNBC) patient samples. MATERIALS AND METHODS: TNBC samples were confirmed for the absence of hormone receptors (estrogen receptor-ER/progesterone receptor) and human epidermal growth factor receptor-2 or proto-oncogene neu or erbB2 or CD340 by immunohistochemical analysis. Formalin-fixed paraffin-embedded samples of patients were used to collect the total RNA. Then, one-step reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the cancer stemness-related transcript levels in the different samples. The RT-PCR products were analyzed semi-quantitatively on agarose gels. The band intensities of respective samples for different transcripts were analyzed by densitometry. RESULTS: TNBC-confirmed samples had shown increased levels of CD133 transcript than control tissues. Further, elevated CD133 transcripts are correlated with higher transcript levels of NOTCH1/FZD7/transforming growth factor-beta receptor Type III R/patched-1 pathway mediators. CONCLUSIONS: This work has clearly indicated that there is a correlation between CD133 and functional pathways that control cancer stem cells in TNBC. These observations may indicate the possible association between cancer stemness and TNBC malignancy.

Variant Philadelphia translocations in chronic myeloid leukemia: A report of five cases.

The t (9;22)(q34;q11) translocation is found in about 90% of the chronic myeloid leukemia patients. About 5-10% of these patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. We describe five male patients in the chronic myeloid leukemia-chronic phase, with rare variant Philadelphia translocations. All of them had the BCR-ABL fusion gene and responded well to treatment with imatinib mesylate. All the patients are on regular follow-up.

Inflammatory pseudotumor of kidney masquerading as renal carcinoma.

Inflammatory pseudotumor also known as inflammatory fibroblastic tumor is a rare benign tumor, which commonly affects the lung. It is very rarely seen in the genitourinary tract. As the preoperative diagnosis, clinically and radiologically is inconclusive, it is imperative to surgically remove and confirm it on histopathologic examination. We report a case of inflammatory pseudotumor in a 51-year-old male who presented with flank pain and was treated with nephrectomy.

Role of direct immunofluorescence in dermatological disorders.

BACKGROUND: Direct immunofluorescence (DIF) test for tissue-bound autoantibodies, has been found to be of value in the diagnosis of several dermatological disorders. The location and pattern of deposition of immunoreactants helps in classifying various immune-mediated diseases. AIMS AND OBJECTIVES: The aim of this study was to analyze the concordance between the clinical, histopathological and DIF diagnosis in bullous and nonbullous lesions of the skin, and thus determine the impact of immunofluorescence on diagnosis. MATERIALS AND METHODS: A total of 215 skin biopsies performed in suspected immune-mediated vesiculobullous disease, vasculitis or dermatosis, were studied. Histopathological examination was done along with DIF study for deposits of immunoglobulin G(IgG), IgA, IgM, and C3. RESULTS: Direct immunofluorescence was positive in 103/215 cases. There was very good concordance between the clinical, histological and DIF results (observed agreement = 93.4%, κ =0.90, with 95% confidence interval = 0.86-0.94). The overall sensitivity of DIF in immune-mediated skin disorders was 98.0%. DIF was positive in 52/53 cases (98.1%) in the pemphigus group and 24/25 (96.0%) bullous pemphigoid cases. None of the clinically suspected cases of dermatitis herpetiformis showed DIF positivity. A positive lupus band test was seen in 9/9 (100%) cases of lupus erythematosus. DIF was positive in 10/10 (100%) clinically suspected cases of Henoch-Schönlein purpura. In 110 cases, negative DIF results helped to rule out immune-mediated vesiculobullous disorders, lupus erythematosus and vasculitis, and the final diagnosis was made on the basis of the clinical features and/or histopathology. CONCLUSION: Direct immunofluorescence is a useful supplement for the accurate diagnosis of immune-mediated dermatological disorders, and helps to classify various autoimmune bullous disorders. When the clinical features/histopathology are inconclusive, the diagnosis often can be made on the basis of the DIF findings alone. A combination of the clinical features, histopathology and DIF usually gives the best results.

Unusual fungal infections in renal transplant recipients.

Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. The causative agent and the risk factors differ depending on the period after the kidney transplant. Also the incidence varies according to the geographical area. We are reporting three cases of fungal infections in renal transplant recipients. Two of them have etiological agents which are common among immunosuppressed patients, but with an atypical clinical presentation, while one of them is a subcutaneous infection caused by a less frequent dematiaceous fungus, Aureobasidium pullulans. These cases highlight how a high index of clinical suspicion and prompt diagnosis is very much essential for better outcome. The emerging fungal infections and paucity of data regarding their management pose a challenge to the transplant physicians.

Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report.

Angiosarcomas are rare tumors that predominantly affect adults. Hepatic angiosarcoma in a child is extremely rare and associated with a poor prognosis. Herein, we report the pathologic features of a hepatic angiosarcoma developing in a 31/2-year-old child who had been earlier diagnosed and was being treated for hepatic hemangioendothelioma.

Primary Extranodal Lymphomas of Lip - A Rare Manifestation in Sjogren's Syndrome.

Sjogren's syndrome (SS) is a chronic autoimmune disorder which is characterized by lymphocyte-mediated destruction of exocrine glands, which produces the classical symptoms of dry eyes and dry mouth, which is referred to as primary SS or the Sicca complex. When it is associated with another autoimmune disease such as rheumatoid arthritis or lupus erythematosus, the condition is termed as secondary SS. One of the known major complications in patients with Sjogren's syndrome is the occurrence of Non-Hodgkin's lymphoma of B cell type. It is not uncommon for malignant lymphomas to occur in head and neck region at nodal and sometimes, extranodal sites. However, only rarely may they involve the oral cavity primarily. This case report describes a rare occurrence of isolated extranodal lymphomas in the upper and lower lips of a patient, which clinically resembled a mucocele, and eventually was diagnosed as lymphoma which was associated with Sjogren's syndrome, thereby stressing the importance which was played by an oral diagnostician.

Acute-Onset of Multiple Painful Nodules over Forearms and Back.

Angiolipomas are benign encapsulated, well circumscribed tumours, which show excessive degree of vascular proliferation. Clinically, lesions present as sudden onset of multiple painful nodules. Pain usually does not respond to analgesics. We herein, report a case of a young male, presenting with multiple painful nodules over the forearm and back, which on histopathological examination revealed, encapsulated benign tumour, comprising of proliferated small-caliber vascular channels with microthrombi and variable amounts of mature adipose tissue. Pain subsided on treatment with intralesional steroids and the nodules were excised through a narrow-hole extrusion technique.

Hepatic and adrenal hemangioendothelioma-a case report.

Haemangioendothelioma (HE) liver is a mesenchymal vascular tumour, intermediate between a haemangioma and an angiosarcoma. It has a variable clinical course, is a low grade malignancy and is associated with long-term survival. It has a characteristic histologic appearance. Immunohistochemical studies have shown that the neoplastic cells in HE are of endothelial derivation. These are essential to distinguish HE from metastatic carcinoma and primary epithelial liver tumour. We report a case of a 36-year-old male with HE of the liver with adrenal involvement, probably metastatic, with tuberculosis as an incidental finding. To our knowledge this is the first such case reported in literature. The confirmation of diagnosis was done by immunohistochemical study.

Solitary fibrous tumour of the kidney: case report with review of the literature.

Solitary Fibrous Tumour (SFT) is an unusual spindle cell tumour that usually occurs in the pleura, but has recently also been reported to be extra-pleural in origin. A renal presentation is very rare. Upto 90% of the tumours have benign characteristics. It is difficult to differentiate it from renal cell carcinoma by using imaging techniques. A definitive diagnosis can be made by doing a detailed pathological examination, which includes immunohistochemistry. We are reporting a case of a large solitary fibrous tumour of the kidney which here occurred in a 70-years-old male. Histological examination of the resected specimen confirmed the diagnosis, by revealing strongly positive reactions of the neoplastic cells for CD34, bcl-2, vimentin and negativity for Epithelial Membrane Antigen (EMA), Smooth Muscle Actin (SMA), S-100 protein and Ki-67. The patient suffered a cardiac arrest and died on the seventh day after his surgery.

Idiopathic giant cell myocarditis: a case report.

Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. The patients usually die of heart failure and ventricular arrhythmia unless a cardiac transplantation is performed. We are reporting here an autopsy case of idiopathic giant cell myocarditis with no symptoms in a 27-year old -worker who died suddenly.The purpose of this report was to emphasize that idiopathic giant cell myocarditis was a rare disease and that it could exist in the absence of any symptomatic heart disease.

Need for mentorship to improve learning in low-performers.

BACKGROUND: About 15% of medical students perform poorly in examinations. This study was done to ascertain the causes for low performance and the effectiveness of counselling and advice regarding study skills in improving performance in a subsequent assessment. METHODS: Of the 353 students who appeared for the first internal assessment examination in pathology, 83 (23.5%) scored less than 30% marks. These 83 low-performers were given a questionnaire listing stress-inducing factors and academic problems; 81 filled the questionnaire. Of these, 73 attended sessions on study skills and counselling where they interacted on a one-to-one basis regarding their personal problems. Their performance was evaluated in an internal assessment 6 months later. RESULTS: The low-performers included 52 boys and 29 girls, 19-20 years of age. Non-academic problems contributing to low performance included language problems, problems in adjustment to life outside home, lack of self-confidence, fear of failure and worrying about the future. Academic problems included difficulty in managing study time, lack of concentration while studying, inability to retain what is studied, anxiety before examinations and inability to write an examination. Paired t-test revealed a statistically significant improvement in the post-programme performance of the 73 students who participated in the counselling sessions (p<0.001), while that of the 10 who did not participate in the project, showed no statistically significant difference (p=0.54, Wilcoxon signed rank test). A majority of students felt that the sessions helped to improve their performance (average score 3.83/6.00), change their study behaviour (3.74/6.00) and change their attitude (3.46/6.00). The programme also improved their confidence and self-esteem. CONCLUSION: Low-performers can benefit from tailored remedial programmes which include counselling and training in stress-coping strategies.

Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: a rare co-existence with therapeutic dilemma.

A 21 year old female presented with amenorrhea, hirsutism and change in voice along with an elevated serum ß-HCG (human chorionic gonadotrophin) level and normal CA-125 level. Laparotomy revealed an enlarged right ovary measuring 6×5×1 cms with presence of an ovarian hemangioma along with stromal luteinization and HCG producing mononucleate as well as multinucleate cells of uncertain histogenesis on histopathological examination. Immunohistochemistry for inhibin and calretinin were positive in the luteinized component whereas ß-HCG and Ki-67 were positive in the multinucleate cell component. The diagnostic rarity and therapeutic dilemma of such a rare mixed tumor within a single ovary has proven to be an exceptional case and an excellent investigative opportunity.

Opportunistic infections in a renal transplant recipient.

With the present progress in transplantation procedures, there is an improvement in patient and allograft survival. However, the immunosuppression necessary to sustain the allograft predisposes these transplant recipients to infection, which is now a significant cause of morbidity and mortality. We describe a case of a 30-year-old renal transplant recipient with two opportunistic infections, namely, primary cutaneous aspergillosis and intestinal tuberculosis, with terminal enterococcal pleuritis and peritonitis. Control of the degree of immunosuppression, and prompt recognition and treatment of infection are vital for successful organ transplantation.

Sentinel Lymph Node Biopsy in Breast Cancer.

The axillary lymph node status is the most reliable prognostic indicator of recurrence and overall survival in patients with breast cancer. The current standard surgical procedure for the management of invasive breast cancer is the complete removal of the cancer with total axillary clearance. However, recently, selective sentinel lymph node mapping and biopsy is gaining acceptance as a useful and accurate staging procedure, as it is minimally invasive. The sentinel lymph node is the first node into which a primary cancer drains, and is thus the first node to be involved by metastases. Patients whose sentinel nodes are negative for breast cancer metastases, can be spared a more extensive axillary lymph node dissection, with reduction in the postoperative morbidity. Sentinel node mapping is usually performed by intradermal or peritumoral injection of a combination of blue dye and radiotracer. Sentinel node examination is sometimes done intraoperatively, by imprint cytology and frozen sections, for an immediate assessment, to plan the extent of surgery at a single sitting. Permanent sections of the sentinel node are studied by serial sectioning, and immunohistochemistry for cytokeratin is done to detect micrometastases which are frequently missed on hematoxylin and eosin (H&E)-stained sections. The various aspects of sentinel node examination, and its role to decide further management in patients with ductal carcinoma-in-situ, and in other clinical settings, are discussed in this review.

Intraventricular hydatid cyst in a child.

Hydatid disease is caused by the infestation of the larvae of tapeworms of the genus Echinococcus. The definitive hosts of Echinococcus are various carnivores, the common being the dog. All mammals (more often sheep and cattle) are intermediate hosts. Humans get infected through the feco-oral route by ingestion of food or milk contaminated by dog feces containing ova of the parasite or by direct contact with dogs. The most common sites of infestation are the liver (75%) and lungs (15%). Various authors state a frequency of hydatidosis of the brain ranging between only 0.2-4% of cases. [1],[2],[3] The prognosis following surgical intervention is good, especially in pediatric age. [2],[3] Hence early diagnosis of this condition is crucial. We report a rare case of a child with a large intraventricular hydatid cyst that had an excellent recovery following surgery.

Liver histology in patients on hemodialysis with chronic hepatitis C viral infection.

Hepatitis C virus (HCV) is a major cause of chronic liver disease in patients on hemodialysis. As no useful noninvasive predictors of disease activity and fibrosis have been found, liver biopsy is essential in these patients to accurately assess the severity of disease and thus the prognosis and plan management. The present study was undertaken to assess the degree of severity of necroinflammatory changes and fibrosis in liver biopsies of patients on hemodialysis with chronic HCV infection. Liver biopsies obtained from 45 patients on hemodialysis with serological evidence of chronic hepatitis C were studied. The grading of necroinflammatory activity and staging of fibrosis were histologically assessed. The majority of patients (30, i.e. 66.7%) had mild disease with mild inflammatory activity and stage 0, 1 or 2 fibrosis. There was no significant correlation between the degree of fibrosis and the age of the patients (rs = 0.015), the duration of hemodialysis (rs = 0.047) or the presence of steatosis (rs = 0.064). There was a positive correlation between the presence of bile ductular proliferation and the severity of fibrosis (rs = 0.612). It was concluded that chronic HCV infection in hemodialysis patients is relatively mild early in its course. However, serial follow-up liver biopsies are mandatory to plan appropriate intervention strategies.