Vitamin D, a fat-soluble prohormone is synthesized in response to sunlight. Experimental evidence suggests that vitamin D may reduce the risk of cancer through regulation of cellular proliferation and differentiation as well as inhibition of angiogenesis. These anticancer properties have been attributed primarily to 1,25-dihydroxyvitamin D [1,25(OH) ₂ D] (calcitriol), the hormonal form of vitamin D. Extensive research has shown that cells, including cancer cells, express specific receptors (VDR) for 1,25-dihydroxyvitamin D. When bound to the VDR, 1,25-dihydroxyvitamin D regulates >60 genes that exert prodifferentiating, antiproliferative and antimetastatic effects on cells, including effects on cell cycle. The amount of exposure to the sun has been found to correlate inversely with cancer mortality and survival in numerous epidemiological studies. An inverse relationship between solar ultraviolet-B (UV-B) exposure and non-skin cancer mortality has long been reported. Several ecological studies suggest that sunlight may protect against prostate, colon, rectal, female breast and ovarian cancer, all diseases that contribute to a substantially higher proportion of cancer mortality in the western industrialized world. Some analytical studies also suggest a protective association between circulating vitamin D in blood, which is largely derived from sunlight, or dietary vitamin D. Paricalcitol (calcitriol analogue) is as effective as 1,25-dihydroxyvitamin D in transactivating the prostatic VDR and in inhibiting the growth of prostate cancer cell lines and primary cultures of prostate cancer cells in vitro. Promising preclinical evaluations of calcitriol and analogues have appeared in prostate cancer animal models.

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Locally advanced breast cancer (LABC) accounts for a sizeable number (30-60%) of breast cancer cases and is a common clinical scenario in developing countries. The treatment of LABC has evolved from single modality treatment, consisting of radical mutilating surgery or higher doses of radiotherapy in inoperable disease to multimodality management, which along with the above two included systemic therapy. Neoadjuvant chemotherapy (NACT) has made a tremendous impact on the management of LABC. NACT was initiated to institute systemic therapy upfront at the earliest in this group of patients with a high risk of micrometastasis burden. While NACT did not yield a survival advantage, it has however made breast conservation possible in selected group of cases. Large number of studies and many randomised trials have been done in women with LABC in order to improve the therapeutic decisions and also the local control and survival. With this background we have reviewed various treatment options in patients with LABC which should possibly help in guiding the clinicians for optimal management of LABC.

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Aims and Objectives: Aims and objectives of this study are to get the best fit of the normal tissue tolerance doses to the NTCP model of the linear quadratic model. Methods and Materials: To compute the NTCP, the modified form of the Poisson cell kill model of NTCP, based on linear-quadratic model, is used. The model has been applied to compute the parameters of the NTCP model using clinical tolerance doses of various normal tissues / organs extracted from published reports of various authors. The normal tissue tolerance doses are calculated for partial volumes of the organs using the values of above-said parameters for published data on normal tissue tolerance doses. In this article, a graphical representation of the computed NTCP for bladder, brain, heart and rectum is presented. Results and Conclusion: A fairly good correspondence is found between the curves of 2 sets of data for brain, heart and rectum. Hence the model may, therefore, be used to interpolate clinical data to provide an estimate of NTCP for these organs for any altered fractionated treatment schedule.

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Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU), Ellagic acid (EA), Triphala (TPL), Tocopherol Succinate (TOS) and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS) by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC), Human cervical (HeLa) and breast (MCF-7) cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

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Materials at nano dimensions exhibit totally different properties compared to their bulk and atomic states. This feature has been harnessed by scientists from various disciplines, to develop functional nanomaterials for cancer diagnosis and therapeutics. The success stories range from delivering chemotherapeutic molecules in nano-sized formulations to functional nanomaterials, which deliver thermal and radiotherapy at specific targeted sites. This brief review summarizes the recent developments of various nanotechnologies in cancer therapy and diagnostics, both from the research sector and the upcoming products in pipeline on its route to commercialization. Supportive engineering innovations and frontiers in nanomolecular research, with a potential to revolutionize cancer therapy, have been discussed in brief.

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Gastric cancer is one of the most common cancers and most frequent causes of cancer-related deaths in the world. The overall survival rate is 15-20%. Although the incidence is declining, its prognosis remains poor. The etiological factors and pathogenesis of gastric cancer are not yet fully understood. The integrated research in molecular pathology clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of development and progression of gastric cancer. Although epidemiological evidences indicate that environmental factors play a major role in the carcinogenesis, the role of immunological, genetic and immunogenetic factors are thought to contribute to etiopathogenesis of gastric carcinoma. In addition to better understanding of pathogenesis of gastric cancer, the incidence, diagnostic studies and the therapeutic options have also undergone important changes in the last decade. There is ongoing debate regarding the role of adjuvant treatment. In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the newer concepts of molecular biology on gastric carcinogenesis and the new important recommendations for the management of patient with gastric carcinoma.

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Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC) and sphingomyelin (SM) in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student's t-test (p < 0.05) and one-way analysis of variance (ANOVA) was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic component. Conclusion: The Langmuir monolayer technique was sensitive to detect changes in tensiometric profiles of cervical cancers and these could be modulated by alterations in phosphatidylcholine and sphingomyelin levels. Therapeutic strategies may be designed to modulate these tensiometric profiles and lipid constituents of cancerous tissues.

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Background: Hypothyroidism is a known consequence of external beam radiotherapy to the neck encompassing part or whole of the thyroid gland for over 40 years. Still thyroid function tests are not a part of routine follow up of head - neck cancer patients treated with radiotherapy with or without surgery and / or chemotherapy. Aim: Aim of this study was to find out the incidence of hypothyroidism in head - neck cancer patients treated with radiotherapy with or without chemotherapy where radiation portals included most or whole of the thyroid gland. Materials and Methods: From September 2001 to November 2003, 187 patients with head-neck malignancies were treated with external beam radiotherapy whose radiation portals included part or whole of the thyroid gland with / without chemotherapy. Thyroid function tests were done at the beginning of treatment, at six weeks after completion of radiotherapy and thereafter at six weeks interval for two years. Results: Out of 187 patients, five were excluded from the study as they were found to be hypothyroid before the initiation of treatment. Another four were excluded from result analysis because they underwent laryngectomy for uncontrolled disease. Of the patients attending the follow up clinic, 17.8 % and 21.8 % were found to have clinical and sub-clinical hypothyroidism at two year. Conclusion: As a significant number of patients develop hypothyroidism following radiotherapy to the neck, thyroid function tests should be included in the routine follow up protocol of such patients. But certain questions have emerged from this study which need a large randomized study to find out the answers.

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Advances in cancer management have resulted in a significant increase in median survival of number of diseases. Consequently we are seeing more patients living long enough to develop symptomatic brain metastases. The management of such patients will be discussed here. The most important definitive investigation is contrast enhanced MRI scan of brain. Management consists of supportive care and disease directed treatment. Surgical resection remains the gold standard for the treatment of solitary brain metastases. Whole brain radiotherapy is considered standard treatment for all patients with brain metastases. The role of chemotherapy was limited in the past. Recently several new agents have been identified as potentially useful. Preliminary results indicate that drugs like temozolomide and topotecan have antitumor activity against the brain metastases as well as the primary systemic malignancies. The goal of multimodality treatment for brain metastases is to palliate local symptoms and prevent consequences of neurological involvement.

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Hyperthermia is an ancient, but nowadays rapidly developing treatment method in tumor-therapy. Its new paradigm applied in the electro-hyperthermia (oncothermia), which provides energy by means of electric-field and produces non-equilibrium thermal situation in the tissue. The temperature gradients formed in stationer conditions, destroy the membrane of the malignant cells and selectively eliminate the cancer tissue. The characteristic control parameter is the absorbed energy-dose, which is partly used to make the distortions, partly to increase the temperature of the target. This type of technique could be applied for some tumor sites, including brain, soft tissues, liver and abdominal masses, pancreatic cancer, head and neck tumors as well.

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Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (from glycolysis) and NADPH (from the pentose cycle). Furthermore, in cancer cells, glucose deprivation as well as treatment with 2-deoxyglucose (2 DG) has been shown to induce oxidative stress and cytotoxicity. Additionally, transformed cells have been shown to be more susceptible to glucose deprivation (and 2DG-)-induced cytotoxicity and oxidative stress than untransformed cells. These results support the hypothesis that cancer cells have a defect in mitochondrial respiration leading to increased steady state levels of O _{2^• - and H 2 O2} , and glucose metabolism is increased to compensate for this defect. The application of these findings to developing cancer therapies using 2DG combined with inhibitors of hydroperoxide metabolism to induce radio/chemosensitization is discussed, as well as the possibility that FDG-PET imaging may predict tumor responses to these therapies.

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Pharyngocutaneous (PC) fistula is a common complication following laryngectomy. It leads to increased morbidity, delay in adjuvant treatment, prolonged hospitalization and an increase in treatment costs. Although a number of factors that result in PC fistula have been described, there is still no agreement on the most significant factors. We undertook a prospective study to critically analyze PC fistula and its association with various tumors, patient and treatment related factors. This was a prospective study that included 143 patients who underwent laryngeal surgery for squamous cell carcinoma of the larynx and pyriform sinus. Use of pectoralis major myocutaneous flap to reconstruct the neopharynx, primary disease in pyriform and extensive soft tissue infiltration were significantly associated with PC fistula. Prior treatment (radiotherapy and chemotherapy), type of closure (T closure, Y closure and vertical closure), Layers of closure (full thickness interrupted, submucosal interrupted, submucosal continuous) type of suture material (silk, vicryl ), age, sex, stage, preoperative tracheostomy, cut margin status, pre/postoperative hemoglobin and experience of surgeons did not relate significantly.

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Total laryngectomy or laryngopharyngectomy remains the procedure of choice for advanced-stage (UICC T3 and T4) laryngeal carcinoma around the world despite advances in conservative laryngeal surgery and radiotherapy. However, it has profound effects on respiration and deglutition, in addition to the most disabling effect-the loss of verbal communication. Successful voice restoration can be attained with any of three speech options, namely esophageal speech, electrolarynx, and tracheoesophageal (TO) speech using an artificial valve. Although, no single method is considered the best for every patient, the tracheoesophageal puncture has become the preferred method in the past decade. Several types of voice prostheses have been produced since the first prosthesis was introduced in 1980 by Blom and Singer. However, eventually all prostheses are confronted by the same problem, i.e., the development of a biofilm, leading to deterioration and ultimately to dysfunction of the prostheses, necessitating replacement. This article attempts to sum up the historical background as well as the current state of surgical voice rehabilitation following laryngectomy; we review the recent major advances as well as the future prospects. Data was collected by conducting a computer-aided search of the MEDLINE and PubMed databases, supplemented by hand searches of key journals. Over 50 articles published in the last three decades on the topic have been reviewed, out of which about 20 were found to be of relevance for this article.

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We shall assume, of course, that the objective of hyperthermia is to destroy the malignant cells. Destruction definitely needs energy. Description and quality assurance of hyperthermia use the Pennes heat equation to describe the processes. However the energy balance of the Pennes-equation does not contain the hyperthermic cell-destruction energy, which is a mandatory factor of the process. We propose a generalization of the Pennes-equation, inducing the entire energy balance. The new paradigm could be a theoretical basis of the till now empirical dose-construction for oncological hyperthermia. The cell destruction is a non-equilibrium thermodynamical process, described by the equations of chemical reactions. The dynamic behavior (time dependence) has to be considered in this approach. We are going to define also a dose concept that can be objectively compared with other oncological methods. We show how such empirical dose as CEM43oC could be based theoretically as well.

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Purpose : This study was mainly framed to study the difference in tumor volumes as seen on computed tomography (CT) and magnetic resonance (MR) and their significance in planning. Materials and Methods : Twenty-five patients with brain tumor of different diagnoses who underwent stereotactic radiotherapy were included in this study. CT and MR imaging was done for all the patients with 2.5 mm slice thickness. The CT tumor volume and MR tumor volume were measured and compared with each other. The center of mass (CM) of the tumor volume delineated on CT and MR were computed and the shift between the two CMs was determined. Results : The mean and median volume of the tumor as measured from MR scans was 19.67 cc ± 13.73 and 16.13 cc (range: 3.25 cc - 50.37 cc). Similarly, the mean and median volume of the tumor as measured from CT scans was 15.05 cc ± 10.13 and 11.63 cc (range: 3.0 cc - 36.25 cc) respectively. The mean and median CM shift between CT and MR was 5.47 mm and 5.21 mm respectively. Conclusion : The study demonstrates that MR is an indispensable imaging modality in radiotherapy for planning brain tumors.

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Gardasil^® is the first quadrivalent human papillomavirus (HPV)- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

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Nasopharyngeal carcinoma (NPC) differs from other head and neck cancers in its epidemiology, natural behavior and, particularly, in the therapeutic considerations. In addition, NPC is responsive to both chemotherapy and radiotherapy (RT). This article reviews the recent advances in concurrent chemoradiotherapy (CCRT) for NPC. To identify the studies mentioned in this article, we searched the MEDLINE database, and abstracts of selected conference proceedings (up to 2008) using the key words 'nasopharyngeal carcinoma,' 'advanced,' 'radiotherapy,' and 'concurrent chemotherapy.' Eight randomized clinical trials of CCRT in NPC have been reported in the English literature. These trials can be classified according to the timing of the chemotherapy, which was given either concurrently with RT (in three trials) or concurrently with radiotherapy and adjuvant after the and of concurrent chemoradiotherapy (in five trials). There have also been four meta-analyses addressing the value and scheduling of chemotherapy in the curative treatment of NPC. This article reviews the recent literature and the pertinent issues concerning the role of CCRT in the treatment of patients with locoregionally advanced NPC.

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the Indian subcontinent. Although tobacco and alcohol are the main etiologic factors for nearly three-fourth of these cancers, no definite etiologic factor can be identified in one-fourth of the cases. There is growing evidence that human papilloma virus (HPV) may act as a cocarcinogen, along with tobacco, in the causation of oral cancers. The role of HPV in the etiology of anogenital cancers has been firmly established, and infection with this virus has also been shown to have prognostic significance. However, there is no clear evidence to support its involvement in oral carcinogenesis. We searched the PubMed database for all literature published from 1985 to 2008 and performed a systemic review in order to understand the relationship of HPV with oral cancers and its prevalence in various sub-sites in the oral cavity. Association of HPV is strongest for oropharyngeal cancers, especially cancers of the tonsils, followed by those of the base of tongue. High-risk HPV-16 is the predominant type; it commonly affects the younger age-groups, with males appearing to have a predisposition for infection with this strain. Its prevalence increases from normal to dysplasia and finally to cancer. HPV prevalence has been reported to be twice as high in premalignant lesions as in normal mucosa and is nearly five times higher in OSCC. The overall prevalence of HPV in OSCC ranges between 20-50%. OSCCs associated with HPV have been found to have better outcomes, being more responsive to radiotherapy and showing higher survival rates. In view of the association of HPV with OSCC, it should be worthwhile to conduct further experimental studies to elucidate its role in oral carcinogenesis.

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Context: Accelerated partial-breast irradiation (APBI) using various approaches is being increasingly employed for selected women with early breast cancer (EBC). Aims: To conduct a case-control study comparing disease control, cosmesis, and complications in patients with EBC undergoing APBI using multicatheter interstitial brachytherapy vs those receiving conventional whole breast radiotherapy (WBRT). Settings and Design: Women with EBC fulfilling the American Brachytherapy Society (ABS) criteria were selected as 'cases' if treated with APBI or as 'controls' if offered WBRT during the period from May 2000 to December 2004. Materials and Methods: APBI patients were treated with high-dose-rate brachytherapy (HDR) to a dose of 34 Gy/10#/6-8 days. WBRT was delivered to the whole breast to a dose of 45 Gy/25# followed by tumor bed boost, either with electrons (15 Gy/6#) or interstitial brachytherapy (HDR 10 Gy/1#). Results: At the median follow-up of 43.05 months in APBI and 51.08 months in WBRT there was no difference in overall survival (OS), disease-free survival (DFS), late arm edema, and symptomatic fat necrosis between the two groups. However, APBI resulted in increase in mild breast fibrosis at the tumor bed. Telangiectasias were observed in three patients of the APBI group. The cosmetic outcome was significantly better in the APBI group as compared to the WBRT group (P = 0.003). Conclusions: This study revealed equivalent locoregional and distant disease control in the two groups. APBI offered better overall cosmetic outcome, though at the cost of a slight increase in mild breast fibrosis and telangiectasias.

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Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB) in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0) Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients). Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

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Brain metastases are a significant cause of morbidity and mortality in patients with breast cancer. HER-2 positivity is an increasingly recognized risk factor for the development of brain metastases. Although considerable progress has been made in the treatment of this complication, supportive measures like steroids, anti-seizure medication and whole-brain radiation remain the cornerstones of management in the majority of patients. The current review discusses the above and other issues like surgical excision, stereotactic radiotherapy, adjuvant radiation, radiosensitization and chemotherapy. A brief discussion of the recent evidence for the use of 'HER-1/ HER-2'-targeted therapy is also present.

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Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.

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An eleven-year-old boy presented with a swelling in his left elbow. Radiologically the features were that of an Ewing's sarcoma involving the ulna. Histopathology showed small round cell tumor strongly positive for Monoclonal Imperial Cancer research fund 2 (MIC2) antigen. Similar cells in the bone marrow were involved with MIC2 positivity. The patient developed skin lesions, which on biopsy were found to be chloromas. The initial biopsies were reevaluated with special stains revealing granulocytic sarcomas in acute myeloid leukemia masquerading as Ewing's due to its MIC2 positivity. The possibility of myeloid neoplasms should be considered routinely with known MIC2 positive round cell tumors.

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Higher rates of glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo) have shown that 2-deoxy-D-glucose (2-DG), a glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral glioma tissues, clinical trials were designed taking into consideration the radiobiology of gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg body weight orally administered after overnight fasting, 20min before irradiation) with large weekly fractions (5 Gy/fraction) of low-LET radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to hypoglycemia induced disturbances like restlessness, nausea, and vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.

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