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http://www.webmedcentral.com/images/Header_Logo.giftext/html2010-09-18T10:08:28+01:00http://www.webmedcentral.com/Mr. Balram SoniExperimental Cancer Treatment: An Emerging Approach
http://www.webmedcentral.com/article_view/656
CancerCancer is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize.CausesCancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. These abnormalities may be due to the effects of environmental risk factors such as UV radiation, viruses including hepatitis B and C, human papilloma viruses (HPV), chemicals, alcohol, high cholesterol diets or infectious agents, hereditary risk factors, hormonal imbalances and immune system dysfunction.What Are the Options in Treating CancerThe journey with cancer is a long, stressful and strenuous one. The treatment procedure itself may be detrimental to the emotional well-being of the patient. This is where complementary and alternative therapies have stepped in to offer holistic treatment. Complementary and alternative medicine (CAM)—also referred to as integrative medicine—includes a broad range of healing philosophies, approaches and therapies. These therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms.The terms "complementary" and "alternative" are often used interchangeably, when in fact they are two different therapies. Complementary therapies such as acupuncture, aromatherapy, art therapy, counseling, massage, meditation, etc. are therapies which are given alongside conventional cancer treatments. The former, however, does not replace the latter. They play a supportive role and are only used in addition to standard treatments. Some commonly used methods of complementary therapy include mind-body control interventions such as visualization or relaxation; manual healing, including acupressure and massage; homeopathy; vitamins or herbal products; and acupuncture. Alternative therapies, on the other hand, are used instead of conventional treatments. Electromagnetic therapy, essiac (a mixture of herbs), iscador (mistletoe extract) and gerson therapy are some examples of alternative treatments.Traditional or conventional treatmentTraditional or conventional treatment options may include surgery, chemotherapy, radiation, immunotherapy and hormonal therapy. These therapies have all been tested in clinical research trials and proven to be acceptable, safe and effective, although with often unpleasant side effects.1. Surgery:Surgery can cause certain side effects such as surgical anxiety, bleeding problems, blood clots (deep vein thrombosis), death, difficult breathing and infections after surgery.2. Chemotherapy: Chemotherapy can cause side effects like hair loss, an upset stomach, and sexual side effects such as loss of labido, erectile dysfunction, vaginal dryness, vaginal infections, and dehydration symptoms.3. Radiation therapy:Radiation therapy uses certain types of energy to shrink tumors or eliminate cancer cells.High levels of radiation like those from radiation therapies and x-rays can damage normal cells and increase the risk of developing leukemia, as well as cancers of the breast, thyroid, lung, stomach and other organs.4. ImmunotherapyCurrently the vaccine is not recommended for pregnant women. It may cause soreness around the injection area.5. Hormonal therapyRemoving or blocking estrogen or testosterone for treatment is a major drawback associated with hormonal therapy.Experimental cancer treatments These are medical therapies intended or claimed to treat cancer by improving on, supplementing or replacing conventional methods (surgery, chemotherapy, radiation, hormonal and immunotherapy). Experimental cancer treatments include:1. Bacterial treatments Chemotherapeutic drugs have a hard time penetrating tumors to kill them at their core because these cells may lack a good blood supply. Researchers have been using anaerobic bacteria, such as Clostridium novyi, to consume the interior of oxygen-poor tumors. These should then die when they come in contact with the tumor’s oxygenated sides, meaning they would be harmless to the rest of the body.Another strategy is to use anaerobic bacteria that have been transformed with an enzyme that can convert a non-toxic prodrug into a toxic drug. With the proliferation of the bacteria in the necrotic and hypoxic areas of the tumor, the enzyme is expressed solely in the tumor. Thus a systemically applied prodrug is metabolized to the toxic drug only in the tumor. This has been demonstrated to be effective with the non pathogenic anaerobe Clostridium sporogenes [1].2. Photodynamic therapyPhotodynamic therapy is generally a non-invasive treatment using a combination of light and a photosensitive drug. Photodynamic therapy uses photosensitive drugs such as 5-ALA, Foscan, Metvix, Tookad, WST09, WST11, Photofrin and Visudyne which are triggered by light of a specific wavelength.3. HAMLET (human alpha-lactalbumin made lethal to tumor cells)HAMLET is a molecular complex derived from human breast milk that kills tumor cells by a process resembling programmed cell death. HAMLET causes apoptosis and tumor cell death in tumor cells. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer [2].4. Gene therapyIntroduction of tumor suppressor genes into rapidly dividing cells has been thought to slow down or arrest tumor growth. Adenoviruses are a commonly utilized vector for this purpose. Much research has focused on the use of adenoviruses which cannot reproduce, or reproduce only to a limited extent, within the patient to ensure safety via the avoidance of cytolytic destruction of noncancerous cells infected with the vector. However, new studies focus on adenoviruses which can be permitted to reproduce, and destroy cancerous cells in the process, since the adenoviruses' ability to infect normal cells is substantially impaired, potentially resulting in a far more effective treatment [3,4].5. Telomerase therapyBecause most malignant cells rely on the activity of the protein telomerase for their immortality, it has been proposed that a drug which inactivates telomerase might be effective against a broad spectrum of malignancies. Currently, Inositol hexaphosphate, which is available over-the-counter, is undergoing testing in cancer research due to its telomerase-inhibiting abilities [5].Geron Corporation is currently conducting two clinical trials involving telomerase inhibitors. One uses a vaccine (GRNVAC1) and the other uses a lipidated drug (GRN163L).6. Hyperthermia therapyLocalized and whole-body application of heat has been proposed as a technique for the treatment of malignant tumors. Intense heating will cause denaturation and coagulation of cellular proteins, rapidly killing cells within a tumor.There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound (FUS or HIFU), microwave heating, induction heating, magnetic hyperthermia or direct application of heat through the use of heated saline pumped through catheters. Experiments have been done with carbon nanotubes that selectively bind to cancer cells. Lasers are then used that pass harmlessly through the body, but heat the nanotubes, causing the death of the cancer cells. Magnetic hyperthermia makes use of magnetic nanoparticles, which can be injected into tumors and then generate heat when subjected to an alternating magnetic field [6].7. Dichloroacetate (DCA) Dichloroacetate has been found to shrink tumors in vitro in rats [7]. These studies received attention in the media [8] and some doctors began controversially using the chemical off-label [9]. A small clinical trial has been planned with patients originating from the Edmonton area [10, 11].8. QuercetinIn vitro, quercetin shows some antitumor activity. Cultured skin and prostate cancer cells showed significant mortality (compared to nonmalignant cells) when treated with a combination of quercetin and ultrasound [12].9. Non-invasive RF cancer treatment This preclinical treatment involves using radio waves to heat up tiny metals which are implanted in cancerous tissue. Gold nanoparticles or carbon nanotubes are the most likely candidate. Promising preclinical trials have been conducted [13, 14].10. Insulin potentiation therapyIn IPT, insulin is given in conjunction with low-dose chemotherapy. Its proponents claim insulin therapy increases the uptake of chemotherapeutic drugs by malignant cells, permitting the use of lower total drug doses and reducing side effects. Some In vitro studies have demonstrated the principle of IPT [15, 16].text/html2021-04-19T07:02:05+01:00http://www.webmedcentral.com/Dr. Esther Una CidonEGFR TKIs IN NON-SMALL CELL LUNG CANCER: HEAD AND TAIL OF THE COIN
http://www.webmedcentral.com/article_view/5708
TKIs against the human EGFR have become standard of care for patients with advanced EGFR mutant NSCLC. But despite the initial good results with first generation EGFR TKIs, patients’ cancers will progress after a median duration of response of around 12 months. And some patient will not even show response or only for a short time.
These are due to the development of resistance. Significant research has tried to understand the mechanism behind these two different types of resistance to be able to overcome it with the development of newer drugs. Different generations of TKIs are currently approved to use in routine clinical practice but further investigations need to be carried out to ascertain the best approach to this significant group of patients to be able to extend their cancer natural history with good quality of life.
This article will review the timeline of development of EGFR-TKIs and the mechanism behind the emerging resistance to be able to understand where are we know and where our efforts should be directed.text/html2020-08-17T07:56:51+01:00http://www.webmedcentral.com/Dr. Esther Una CidonMetastatic colon cancer: is rechallenging still an option beyond second line? A quick review.
http://www.webmedcentral.com/article_view/5626
Metastatic colorectal cancer continues to be very frequent and although the improvements in its systemic treatment throughout the past decade have been noticeable, much needs still to be done. Patients’ survival has been prolonged with good quality of life, being still suitable for further treatment, thus further options are expected and demanded by them. The fact is that in heavily treated patients, therapy options are lacking. Beyond second-line, there is no optimal treatment and many have tried a reintroduction of previous chemotherapeutic regimens or biological treatments (such as epidermal growth factor receptor (EGFR) inhibitors used in pretreated patients) although limited evidence exists. Trifluridine/tipiracil has shown a benefit in overall survival when administered to patients who failed on previous chemotherapy and biological treatments. Regorafenib was approved by the US Federal Drug Administration for these patients and no difference has been found between these last two options. Concepts have changed then and a multiline strategy has been defended. What we need is a better knowledge about tumour biology and predictive factors of response so a tailored treatment could be possible one day. At this time we should aim for further strategic clinical trials which seem to be urgently needed.text/html2020-10-07T04:51:06+01:00http://www.webmedcentral.com/Dr. Esther Una CidonRECURRENT PULMONARY EMBOLISM IN METASTATIC BREAST CANCER: RESPONDING TO A DOSE REDUCTION OF ANTICANCER TREATMENT
http://www.webmedcentral.com/article_view/5656
Venous thromboembolism (VTE) is a major complication in cancer patients despite anticoagulation. In fact this is the second cause of death in them, only behind the malignancy itself. Therefore, optimal treatment is crucial.
Low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been included as therapeutic options based on clinical trials.
But the issue here is that there are other contributing factors to the VTE apart from the cancer, such as the anticancer treatment. In fact, the recent incorporation of CDK4/6 inhibitors, such as Palbociclib, has shown to increase these episodes.
We present a case of multiple recurrences of VTE despite anticoagulation, which only responded after a reduction in the dose of Palbociclib.
This should change clinicians’ perspective at the time of treating recurrent VTEs in this population and think promptly about a dose reduction of the anticancer treatment if known to be associated to VTE. text/html2021-01-12T03:39:39+01:00http://www.webmedcentral.com/Dr. Esther Una CidonTriple negative breast cancer under neoadjuvant treatment: the role of assessment ultrasound.
http://www.webmedcentral.com/article_view/5687
Triple-negative breast cancer is a separate entity that comprises several molecular subtypes driven by specific genetic alterations that might potentially be targeted. However, currently most patients continue to receive standard chemotherapy regimens.
Neoadjuvant treatment is accepted for larger tumours and locally advanced disease as it might offer surgical and oncological advantages; among them, it allows a live assessment of tumour sensitivity to treatment, leading to a prompt discontinuation of ineffective therapies to avoid unnecessary toxicities.
It is well known that TNBC is very responsive to chemotherapy, with high rates of pathologic complete responses that can also be quite rapid.
In this scenario, an accurate assessment of residual tumour size and extension becomes crucial for an adequate surgical planification and a prognostic prediction.
Patients should be assessed before, half-way through neoadjuvant chemotherapy and at the end of this treatment. It seems that MRI is the most accurate technique to assess this, but ultrasound and mammogram are the most widely used.
In this context of uncertain diagnosis, we decided to evaluate our results in an audit of TNBC patients receiving neoadjuvant treatment. Our aim was to know the role of ultrasound alone in assessing the pathological response in our patients. text/html2010-09-12T00:29:09+01:00http://www.webmedcentral.com/Mr. Saber BoutayebAdenoma Of The Nipple In A Man: Case Report
http://www.webmedcentral.com/article_view/605
Adenomatosis (adenoma, papillary adenoma, florid papillomatosis) of the nipple is a rare benign disorder involving the nipple witch can be mistaken clinically for Paget's disease and pathologically be misinterpreted as an adenocarcinoma. It occurs mostly in middle-aged women and is extremely rare in adolescents and children. Adenomatosis of the nipple is a well-known in women, but extremely rare in males.We report a 55-year-old man with an adenomatosis of the nipple evolving positively after surgery.text/html2010-09-13T19:06:03+01:00http://www.webmedcentral.com/Dr. Julien ReyalHow could a Basic Knowledge of Vascular Physiology Provide a New Tool for Tumor Oxygen-induced Radiosensitization- Postocclusive Reactive Hyperemia Concept for Synchronized Radiotherapy
http://www.webmedcentral.com/article_view/604
Tumor angiogenesis leads to the development of pathologic vessels and blood flow insufficiency that results in tumor hypoxia, which can be an obstacle for effective radiotherapy. Tumor perfusion enhancement, through increased oxygenation, is a recognized method for tumor radiosensitization, but no clinically efficient means to achieve this have been reported to date.Since tumor-feeding arterial vessels are normal host vessels, postocclusive reactive hyperemia, a well-known physiologic phenomenon in which blood flow rises secondary to the release of arterial occlusion, could be used judiciously in order to temporarily increase the perfusion and oxygenation of a tumor situated downstream of an arterial occlusion site. Perivascular or endovascular vascular occlusion can easily be adapted to each tumor location or size, for easy synchronization of ionizing radiation to the tumor oxygenation peak, either acutely or chronically (i.e., repeated episodes of occlusion, reperfusion and reoxygenation).Thus, postocclusive reactive hyperemia could be an ideal method for tumor perfusion enhancement, as it may combine the desirable characteristics of selectivity, reversibility, and predictability and it can be applied widely throughout the body.text/html2010-09-24T19:06:05+01:00http://www.webmedcentral.com/Dr. Maria Jesus Ramirez-ExpositoDifferential effects of estradiol and tamoxifen on pyrrolidon carboxypeptidase activity in the human estrogen-dependent and estrogen-independent breast cancer cell lines MCF-7 and EVSA-T
http://www.webmedcentral.com/article_view/738
Pyrrolidon carboxypeptidase (Pcp) (E.C 3.4.19.3) is an omega peptidase widely distributed in animal fluids and tissues, which hydrolyzes N-terminal pyroglutamic residues from biologically active peptides such as gonadotropin releasing hormone (GnRH). Previous results obtained in our laboratory showed a decrease of Pcp activity in human and rat breast cancer, suggesting that this enzymatic activity or its putative substrates may play a mayor role in breast cancer pathogenesis. In the present work, we analyze the effects of estradiol and tamoxifen on both Pcp activity and cell proliferation, in the estrogen-dependent and estrogen-independent breast cancer cell lines MCF-7 and EVSA-T. We found a stimulant effect of estradiol on MCF-7 but not on EVSA-T cells growth, whereas tamoxifen inhibited cell growth in both cell types. In the same way, we found a decrease on Pcp activity on MCF-7 cells treated with estradiol, whereas no effect was observed with tamoxifen. Contrarily, Pcp activity also decreased on EVSA-T cells when treated with tamoxifen, whereas no changes were observed in this cell line when treated with estradiol. We propose that Pcp activity and, therefore, its peptide substrate/s (mainly GnRH, but also TRH, neurotensin and bombesin) participates differentially in the pathogenesis of estrogen-dependent and estrogen-independent tumors, and could be considered a target for drug design and development against mammary tumors.text/html2010-10-27T13:56:16+01:00http://www.webmedcentral.com/Mr. Muath HelalDiaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells
http://www.webmedcentral.com/article_view/1081
Metal complex Schiff base compounds have been shown to be cytotoxic in vitro. However little is known concerning anticancer activity of Schiff bases that lack metal cations. The antineoplastic properties of two isomeric derivatives of diaminobenzene bis-Schiff base compounds, namely: N,N'-Bis(2-hydroxy-3-methoxybenzylidene)-1,2-diaminobenzene (2MJ) and N,N'-Bis(2-hydroxy-3-methoxybenzylidene)-1,3-diaminobenzene (2MH) towards U937 and K562 leukemia cell lines were investigated in this study. Both compounds were more cytotoxic towards U937 lymphoma cell with little effect on K562 cells when analysed using Sodium 3′-[1-(phenylamino-carbonyl)-3,4-Tetrazolium]-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) cell proliferation assay technique . The IC50 value for 2MJ was almost half of 2MH . Both compounds were also found to induce apoptosis in U937 leukemia cells as evidenced by the induction of caspase 3 and 7. The level of caspase 3/7 induction was more pronounced in cells treated with 2MJ compared to 2MH. Caspase-9 was identifiedas the regulatory upstream caspase activated in U937 cells treatedwith 2MH and 2MJ, implicating the mitochondrial apoptoticpathway in diaminobenzene Schiff base-induced leukemia cell death. Both agents caused negligible effect on caspase-8 indicating a non Fas ligand receptor involvement in the apoptosis cascade. Neither compounds showed significant mutagenic outcome in the AMES mutagenicity assay. The result of this study highlights the potential of diaminobenzene bis-Schiff base compounds as a prospective agent to target cancer cells via the mitochondria.text/html2010-12-13T15:01:05+01:00http://www.webmedcentral.com/Dr. Mohamed Khadeer Ahamed BasheerMedicinal Potentials Of Orthosiphon Stamineus Benth
http://www.webmedcentral.com/article_view/1361
Orthosiphon stamineus Benth. is a medicinal herb belonging to the family Lamiaceae, grown in Southeast Asia. Leaves of this plant are used commonly in Southeast Asia and European countries for herbal tea, well known as “Java tea”. Traditionally leaves of this plant have been used as diuretic, and to treat rheumatism, abdominal pain, kidney and bladder inflammation, edema and gout. Studies have shown that the O. stamineus leaves exhibit a range of pharmacological properties such as, anti-inflammatory, antioxidant, anti-bacterial, antiangiogenetic properties. Above all, the plant has synergistic bio-enhancing ability for tamoxifen against human breast cancer. The herb has been shown to be exceptionally safe with no toxicity in vitro and in vivo. This review emphasizes the systematic investigation in pharmacological properties of O. stamineus, which could be the potent source of novel herbal curative medicine for critical human diseases.text/html2011-01-22T23:01:30+01:00http://www.webmedcentral.com/Dr. William J MaloneyThe Medical Legacy Of George Herman Babe Ruth
http://www.webmedcentral.com/article_view/1487
Babe Ruth was one of the most beloved and recognized figures of American life in the twentieth century. Ruth rose like a phoenix from the most humble of origins to eventually take his rightful place among the most revered and cherished individuals the world has yet encountered. Ruth’s initial rise to fame was a direct result of his superhuman prowess on the baseball diamond but, his iconic status could not have been achieved without his humanitarian efforts to inspire and raise the quality of life for his fellow man.Endless examples of Ruth’s charitable works abound but no where is his concern for humanity more evident than in the final two years of his life (1946-1948). Ruth was fighting a valiant battle against nasopharyngeal carcinoma. The cancer was exacting a horrible toll on Ruth but, he bravely accepted experimental cancer therapy in order to help medical research gain valuable information to treat individuals with this relatively rare form of cancer in the future.The medical community, in particular, and the population, in general, today directly benefit from the medical information garnered from the medical research performed on this very willing superstar. Ruth remains an inspiration today and a reminder of the tremendous contribution human research subjects make to our wealth of medical knowledge.George Herman "Babe" RuthRuth was born on February 6, 1895 (1) to a couple of German ancestry in Baltimore, Maryland. Ruth’s parents were hard-working tavern owners who had little time to control their energetic and adventurous son. Ruth’s father, on June 13, 1902, brought young George to St. Mary’s Industrial School for Boys. St. Mary’s was located only a few miles south of the Ruth family home but provided a life for George which greatly contrasted with the life he had previously known on the rough waterfront streets of Baltimore . St. Mary’s was run by the Xaverian Brothers who provided discipline, order, and love for the children in their care. George was particularly fortunate to have been placed under the mentorship of Br. Matthias. Br. Matthias was a physically large man with an equally large heart. He introduced George to the game of baseball. George thrived at St. Mary’s and his almost supernatural talent at baseball soon became evident to everyone. His first home run was hit at the amazingly young age of 7 over the right fielder’s head (2).George was recruited to play professional baseball and soon became known as “Babe” to the world. He started his major league career with the Boston Red Sox and was later traded in the most infamous of all sports trades to the rival New York Yankees. It was with the Yankees that Ruth became a most beloved international celebrity. All the while Ruth always remembered the lessons of humanitarianism and charity that he had learned so well during his days at St. Mary’s.On June 7, 1921 his most precious daughter, Dorothy, was born. Dorothy was Babe’s only biological child and was a most faithful daughter to Babe throughout his life. Dorothy wrote of her times with her father in her book, “My Dad, the Babe: Growing up with an American Hero” (3). She would aid her father on his multitude of visits to children in hospitals throughout the world and would continue to spread Babe’s message of charity long after his death until her own passing on May 18, 1989.Many of Ruth’s individual major league baseball records still stand seventy five years after his retirement from the sport. Among these records are most total bases and highest slugging percentage.Nasopharyngeal CarcinomaNasopharyngeal carcinoma (NPC) is a relatively rare cancer in the United States. However, it is a leading form of cancer in middle-aged natives of southern China, southeast Asia, the Arctic, North Africa, and the Middle East (4). The risk factors for NPC include viruses, genetic factors, the consumption of salted fish (5), and environmental factors (6).NPC occurs more frequently in men than in women and is most frequently diagnosed in the sixth decade of life.The Initial Treatments and Misdiagnoses of RuthRuth suffered through many misdiagnoses at various hospitals in New York City at the onset of his symptoms. In September of 1946 Ruth presented to the French Hospital with the left side of his face swollen and his left eye completely shut. He was diagnosed with either a toothache or sinusitis and his treatment consisted of penicillin and the extraction of three teeth.In November of 1946 his physicians, again at the French Hospital, diagnosed his condition as Horner Syndrome when a radiograph revealed a large mass at the base of his skull (7).Ruth was later misdiagnosed once again as having laryngeal carcinoma based on his supposed history of heavy alcohol and tobacco consumption. Ruth underwent Radiation Therapy in November of 1946 and then, in December of 1946, he underwent unsuccessful surgical resection of the tumor. This surgery left him unable to swallow thus requiring a feeding tube (7).Dr.Richard Lewisohn Richard Lewisohn was born on July 12, 1875 and received his medical education at the University of Freiburg (8).Dr. Lewisohn made many contributions to medicine during his long career, primarily at New York’s Mt. Sinai Hospital. His most well-known contribution is the introduction of the modern technique of blood transfusion (8). In 1947, Dr. Lewisohn was experimenting with an anti-cancer drug, teropterin (9)(pteroltriglutamic acid). However, to this point all his research was performed on mice. He was working with various teropterins, all of which were extracted from brewer’s yeast. The particular preparation of the teropterin caused a wide variation in the effects seen on the mice (9).Dr. Lewisohn offered Ruth to receive this experimental therapy. Dr. Lewisohn was very honest with Ruth about his chances for a recovery although no formal informed consent was signed. Dr. Lewisohn told Ruth that receiving this drug probably would not help him and, in fact, might even make his condition worse. Ruth responded bravely that he would still like to go through with the experimental treatment in order to provide the medical community with information that might help individuals in the future with the same ailment. Thus, Ruth became a subject in one of the first clinical trials of an anti-cancer drug (10). Dr. Lewison’s experimental course of teropterin injections led to a dramatic, albeit short-lived, improvement in Ruth (11). The improvement in Ruth’s condition was featured in the lead story of September 11, 1947 in the Wall Street Journal which reported on Dr. Lewisohn’s report of the case at a medical conference. The Wall Street Journal stated that researchers might be on the verge of a cure for cancer (12). Ruth was able to say farewell to his fans at Yankee Stadium and attend other public functions as a direct result of Dr. Lewisohn’s treatment. Babe passed away on August 16, 1948. Dr. Lewisohn passed away 13 years later on August 11, 1961 at the age of 86.text/html2011-01-26T20:34:28+01:00http://www.webmedcentral.com/Dr. Hari D KhannaExpression Of Soluble Toll- Like Receptors And Its Correlation With The Oxidative Damage In Diseased Conditions
http://www.webmedcentral.com/article_view/1480
Infections caused by different pathogens are often associated with systemic symptoms and may compromise the functional integrity. In the mediation of the systemic effect of pathogens Toll-like receptors (TLRs) play a significant role. TLRs are a type of pattern recognition receptor and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. TLRs are broadly distributed on cells of the immune system and function as primary sensors of invading pathogens. There is also growing experimental evidence indicating that Toll-like receptors are expressed on different non-immune cell types as well, like epithelial or endothelial cells.Oxidative stress significantly up-regulate the expression of these receptors whereas TNF-alpha up-regulates the expression of TLR2 and TLR3. Furthermore the activation of TLR2/6 leads to an increased permeability which is accompanied by a down regulation of occludin and claudin-5 expression and disappearance of these tight junction proteins from the cell membrane.Cell biology of TLRs provides new opportunities for drug development for drug intervention to manipulate immune responses. TLRs are mostly associated with initiation of the innate response and inflammation, and inhibition of TLR activity- which may help combat an over active innate response characteristic of numerous inflammatory disorders.text/html2011-02-08T21:38:27+01:00http://www.webmedcentral.com/Dr. Ulrich A PachmannComparing Sequential Steps For Detection Of Circulating Tumor Cells: More Specific Or Just Less Sensitive?
http://www.webmedcentral.com/article_view/1490
Background: We compared two surface epithelial antigen (EpCAM)-based approaches for the detection of breast cancer cells present in the circulation.Methods: Blood from 20 breast cancer patients was drawn into standard blood collection tubes (SBCT) and of 7 of these additionally into CellSave® tubes. After erythrocyte lysis of the samples from both systems, cells were stained with FITC-anti-EpCAM and propidium iodide, quantified with an automated microscope and intact cells counted.Results: EpCAM-positive events from 1ml of blood ranged between 2051 and 28875/ml and from SBCT (MAINTRAC® approach) as compared to between 97 and 2343/ml from the CellSave® tubes, indicating a more than 10-fold reduction in EpCAM accessibility by the preservative. Duplicate cell preparations showed a high correlation of R2=0.89 (MAINTRAC®) from SBCT vs. a moderate correlation of R2=0.81 from CellSave® tubes, but a good correlation (R2=0.91) between the events detected from both systems.Between 1/2 and 1/5 of the positive events were viable cells in the MAINTRAC® approach with unequivocal morphology, and a good (R2=0.89) correlation to total events; by contrast, 1/10 to less than 1/100 of the events in the CellSave® tubes were perhaps cells with equivocal morphology no correlation to total events most positive events being non-recognizable cells. Still 30 to 100-fold more cells were recovered than with the CellTrack® Analyzer.Conclusions: The approach without fixative detects considerably more EpCAM-positive events with good cell morphology as compared to the CellSave® fixation where cell morphology is poor. Magnetic bead enrichment further reduces the number of retrieved cells.
text/html2011-02-27T18:50:02+01:00http://www.webmedcentral.com/Dr. Juliana L SchusselAggressive Nasal Extranodal Nk/t Cell Lymphoma: Case Report
http://www.webmedcentral.com/article_view/1634
Objective: Nasal extranodal NK/T-cell lymphoma is a rare aggressive lesion, characterized by a destructive process of the upper respiratory tract that has an unusual and rapid evolution. Diagnosis is often difficult and requires expert clinical examination and analysis of biopsies using immunohistochemistry.Case report: 34 years-old man with no relevant medical history, presented with an asymptomatic necrotizing lesion on palate and nasal obstruction. Two biopsies were performed with no conclusive results. By the third time, atypical lymphoid tissue was found surrounded by intense necrosis. The diagnosis was confirmed by immunohistochemistry. Chemotherapy was the treatment of choice follow by radiotherapy. The patient presented satisfactory evolution but one year after treatment a recidive was detected and patient died 5 months later from lung metastasis.Conclusion:Suspicious ulcerative lesions in the midline head and neck region must have extranodal NK/T-cell lymphoma as differential diagnosis and repeated biopsies should be taken to confirm diagnosis.
text/html2011-03-03T18:52:16+01:00http://www.webmedcentral.com/Dr. Juliana L SchusselSecond Primary Tumor: P53 and Ki-67 Expression in Patients with Oral Squamous Cell Carcinoma
http://www.webmedcentral.com/article_view/1667
Recent technical and scientific advances on oncology allowed increase of patients’ survival, sequelae reduction and prevention of other tumours, including second primary tumours (SPT). Indeed, some individuals with head and neck cancer manage to survive the first primary tumour, but cannot resist the second. For these reasons, studies to evaluate the factors related to SPT development of are greatly heightened. The aim of this study was correlate the immunoexpression of ki-67 and p53 proteins in oral squamous cell carcinoma (SCC) in two groups: Group A patients who suffered from a primary tumour of the mouth, and Group B patients who developed a SPT. All subjects studied had histological diagnoses of SCC and were admitted to the Erasto Gaertner Hospital, Brazil, from 1990 to 2005 – 35 at Group A and 20 at Group B. All patients’ medical records were reviewed, and immunohistochemistry reactions were realized for ki-67 and p53 proteins. Analysis was made using the chi-square test and the Student's t-test. There was no statistically significant difference (p=0.8768) of p53 expression between groups. In contrast, ki-67 expression showed a statistically significant difference (p=0.0519), with Group B presenting higher staining, showing that positivity was associated with an increased risk of SPT development. text/html2011-03-12T13:41:40+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroRole of the Intracellular pH in the Metabolic Switch between Oxidative Phosphorylation and Aerobic Glycolysis - Relevance to Cancer
http://www.webmedcentral.com/article_view/1716
Cellular energy in the form of ATP can be produced through oxidative phosphorylation and through glycolysis. Since oxidative phosphorylation requires oxygen and generates ATP more efficiently than glycolysis, it has been assumed for many years that the presence or absence of oxygen determines that cells generate energy through oxidative phosphorylation or through glycolysis. Although cells must activate glycolysis in the absence of oxygen to produce ATP, it is now accepted that they can activate both glycolysis and oxidative phosphorylation in the presence of oxygen. In fact, normal proliferating cells and tumor cells are known to have a high glycolytic activity in the presence of adequate oxygen levels, a phenomenon known as aerobic glycolysis or the Warburg effect. Recent observations have demonstrated that the activation of aerobic glycolysis plays a major role in carcinogenesis and tumor growth. Understanding the mechanisms involved in the metabolic switch between oxidative phosphorylation and aerobic glycolysis may therefore be important for the development of potential preventive and therapeutic interventions. In this article, we discuss the role of the intracellular pH in the metabolic switch between oxidative phosphorylation and aerobic glycolysis. We propose that, in the presence of adequate oxygen levels, the intracellular pH may play a key role in determining the way cells obtain energy, an alkaline pH driving aerobic glycolysis and an acidic pH driving oxidative phosphorylation.text/html2011-03-16T22:23:57+01:00http://www.webmedcentral.com/Dr. Julien ReyalHow Could a Basic Knowledge of Vascular Physiology Provide a New Tool for Tumor Oxygen-Induced Radiosensitization- Postocclusive Reactive Hyperemia Concept for Synchronized Radiotherapy
http://www.webmedcentral.com/article_view/1372
Tumor angiogenesis leads to the development of pathologic vessels and blood flow insufficiency that results in tumor hypoxia, which can be an obstacle for effective radiotherapy. Tumor perfusion enhancement, through increased oxygenation, is a recognized method for tumor radiosensitization, but no clinically efficient means to achieve this have been reported to date.
Since tumor-feeding arterial vessels are normal host vessels, postocclusive reactive hyperemia, a well-known physiologic phenomenon in which blood flow rises secondary to the release of arterial occlusion, could be used judiciously in order to temporarily increase the perfusion and oxygenation of a tumor situated downstream of an arterial occlusion site. Perivascular or endovascular vascular occlusion can easily be adapted to each tumor location or size, for easy synchronization of ionizing radiation to the tumor oxygenation peak, either acutely or chronically (i.e., repeated episodes of occlusion, reperfusion and reoxygenation).
Thus, postocclusive reactive hyperemia could be an ideal method for tumor perfusion enhancement, as it may combine the desirable characteristics of selectivity, reversibility, and predictability and it can be applied widely throughout the body.text/html2011-09-05T18:09:44+01:00http://www.webmedcentral.com/Dr. Chun Hei Antonio CheungML-IAP (Livin) and Human Cancers: A Recent Review
http://www.webmedcentral.com/article_view/2159
A relatively new member of the inhibitor of apoptosis protein (IAP) family, ML-IAP (Livin), is found to be involved in the apoptotic resistance of tumor cells. Studies on cell lines and patients have suggested the possibility that Livin is a cancer-specific protein. On the other hand, down-regulation of Livin expression by siRNA has been shown to decrease cancer cell viability and drug resistance in vitro and in vivo. Since detailed molecular mechanisms of Livin have been discussed elsewhere, this review will mainly look at the expression of Livin in various cancer cell lines and clinical samples. This review will further discuss the possibility of targeting Livin in cancers in future clinical situations.text/html2011-09-25T15:35:47+01:00http://www.webmedcentral.com/Dr. Naciri SarahA Rare Case of Invasive Breast Lobular Carcinoma Overexpressing Her2
http://www.webmedcentral.com/article_view/2257
Invasive lobular carcinoma (ILC) appears to have distinctive clinical and biologic characteristics compared with Invasive ductal carcinoma (IDC), as the overexpression of HER2.
The association of HER2 positive phenotype with classical ILC is very rare, therefore we present an atypical case of classical ILC overexpressing HER2 in immunohistochemical study (Hercept test HER2 3+).
We describe the case, and propose a literature review of HER2 phenotype positive in ILC breast cancer.text/html2011-11-12T18:29:06+01:00http://www.webmedcentral.com/Prof. Dainius CharaciejusExpansion of CD8+CD44h Lymphocytes During Growth of SL2 Tumors in DBA/2 Mice
http://www.webmedcentral.com/article_view/2460
CD8+ T lymphocytes are critical in the immune response to tumours. Expansion of CD8+ lymphocytes and their accumulation within a tumour is associated with a prolonged survival of cancer patients. CD8+ lymphocyte expansion in tumour-bearing mice can be demonstrated by acquisitions of highly expressed CD44 antigen (CD44h). In this study, we have investigated the levels of CD8+CD44h lymphocytes in peripheral blood during growth of SL2 tumours in DBA/2 mice. The results of our study show that percentages of CD8+CD44h cells in the CD8+ subset were significantly increased in peripheral blood of tumour-bearing DBA/2 mice compared with control mice. However, this expansion of CD8+CD44h lymphocytes does not seem to have antitumour effect, as tumours grow and all tumour-bearing mice die during the second or third week after tumour implantation.text/html2011-11-24T20:11:52+01:00http://www.webmedcentral.com/Dr. Sara I A.latifThe Dilemma of Multiple Primary Tumours (MPMs) as Rare Medical Condition
http://www.webmedcentral.com/article_view/2502
Introduction:Multiple Primary Malignancies (MPMs) were originally described by Billroth in 1889 and defined as two or more independent malignancies in one individual. The diagnostic criteria for MPMs were established by Warren and Gates in 1932. According to this definition, each tumour must be definitely malignant by histopathology, each must be histologically distinct, and the possibility of one being a metastasis from the other must be excluded. (1)Only limited data are available on the incidence of MPMs. Nevertheless, quadruple primary malignancies are extremely rare and have been reported mainly as case studies. The mechanism of MPMs is not fully understood.Some studies suggested that there is a causal relationship between exposures to carcinogens and somatic mutations of specific genes in several malignancies.Mutation of the tumor suppressor gene p53 (TP53) is the most well-known mutation in human carcinogenesis. Recently, there have also been reports that smoking is strongly associated with the specific mutation of TP53 in lung and bladder cancer, and this genetic predisposition might be related to the development of MPMs (2).Another study has shown the prevalence of second primary tumors in patients with a diagnosis of non-small cell lung cancer (NSCLC) in their history or at follow-up. Furthermore, they studied survival in subgroups of those patients. And conclude that nevertheless, patients with a second tumor tend to have an overall better survival rate than patients without second primaries (3).The Hypothesis:Cancer cells have the ability to produce mutant signaling that is only received by mutant receptors, the same way as cancer can control normal cells by secreting a variety of chemokines and also its ability to form new angiogenesis. It might have the ability to control growth and division of other cancer cells by sending inhibitory signaling which can only affect mutant receptors within the cancer cells that originated from different tissue (another primary tumour).Inhibition of another primary tumour will depend on the signaling type and strength that is secreted by the first one (depends also on the amount of dilution within the body fluids), so if the signaling is equivalent to two or more tumours then there will be cancer coexistence or MPMs . But in this case the growth pattern will be in slow rate and will hence increase the patient's survival, thus considering the immune system as third party in the relationship dimension. Also it is very important that the tumour is not initiated by one of tumour viruses because such involvement can give rise to more aggressive type of tumour .This theory explains that although the patient might have the underlying genetic factors and environmental stress to grow multiple types of primary tumour, still it remains as a rare condition. Second primary tumour will only be able to appear after treatment or removal of the first one , as it is suppressed by the inhibitory signaling which produced by the first primary tumour.Evaluation of the hypotheses:To evaluate this hypothesis, we should culture two cancer cell lines known to be from same underlying mutation and provide it with all essential nourishments and ideal growth atmosphere. Then we should culture each cell line at opposite edges of the media. Also we can put pseudo barrier such as nitrocellulose paper to guarantee the exchange of inhibitory signals and to avoid cannibalism. This can give more opportunity for distant inhibitory signaling which can be achieved by dividing the media into two halves, so it can be observed to figure which type of cell lines is dominating. Moreover, the extent of domination can be measured. This will allow us to study the behavior of the two cell lines toward each other, then we can analyze the proteins residues of inhibitory signaling within the media to have more broad scope of dealing with mutant receptors. The trials can be conducted by different methods; either by culturing one of the cell lines before the other or to culture the cell lines at the same time and observe the amount of inhibitory signaling (this experiment can be repeated using different cancerous cell lines with different amount of cells).text/html2011-12-28T13:58:53+01:00http://www.webmedcentral.com/Dr. Bhanu P IyengarMultipotent Astrocytic Stem Cells Identified During Angiogenesis in Melanoma
http://www.webmedcentral.com/article_view/2801
Background: This study is a sequel to a recent finding that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells and into neuronal positive cells during tumor-vascular interaction. The present work, studies the sequence of formation of tumor-vascular complex [TVC] composed of a angiogenic vessel and a perivascular mantle zone [PMZ] of 1 to 5 layers of tumor cells at the tumor-stroma interphase using gold impregnation to identify multipotent astrocytic stem cells [MASC] in this 3D system. Methods: Serial frozen and paraffin sections are stained with HE, for aurophilia and, dopa oxidase; immunostaining for HMB45, nestin [Nes], GFAP, NFP and synaptophysin [Syn]. The presence of MASC is assessed by Nes and GFAP immunopositivity and compared with aurophilia. Positive cells counts in layers L1 to L5 of the PMZ, on serial frozen and paraffin sections have been subjected to Statistical Analysis by ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. Results: A single tumor cell layer ensheathes the angiogenic vessels entering the tumor margins. These perivascular cells show intense aurophilia, and extend dendritic arbors into the outer layers of the mantle zone. Nes and GFAP positivity is seen in the cell bodies and dendritic processes. As further layers are added on, tumor cells show NFP and Syn positivity in L4 & L5 with a transition zone between L2 to L3. Discussion: During tumor-vascular interaction the perivascular radial glial like cells exhibit aurophilia and Nes/GFAP+vity. Sequential changes are highlighted by gold impregnation. Nes, a marker of multi-lineage progenitor cells, identifies them as MASC. The 4th and 5th layers show NFP&Syn+ve positive cells. Thus TVC exhibits embryonic microenvironment as during neurogenesis. Melanoma cell/endothelial coculures could be a source of MASC for therapeutic uses. Aurophilia does not fade easily unlike fluorescence and immunostained material thus opening up interesting possibilities for use in the study of developmental and adult neurogenesis in the brain as well as in the study of neurospheres in culture. Key Words: angiogenesis, aurophilia, nestin, multipotent astrocytic stem cell, tumor-vascular interaction.text/html2012-04-30T18:58:45+01:00http://www.webmedcentral.com/Dr. Sorabh BadayaAn Epidemiological Study of Various Risk Factors For Carcinoma Cervix: A Study From a Tertiary Care Hospital in Gwalior, India
http://www.webmedcentral.com/article_view/3315
Background and Objectives: Worldwide cervical cancer is the fifth most deadly cancer among the women, 80% of which belong to developing countries. Thus it incites us to look into the depth of its various different risk factors and to propose a demanding strategy in its control.Methods: Study consists of a prospective analysis of a total number of 813 women, those underwent gynaecological examination from May-August, 2010 at the outpatient department (OPD), department of Obstetrics and Gynaecology, JA Groups of Hospitals, Gwalior for cervical pap smears, taken as a part of their routine check-up. Reporting of all the pap smears were done for carcinoma cervix in women of all age groups for a comprehensive data based study through pap smears analyses.Results: Smears of the women who were suspected for carcinoma on clinical examination were confirmed by the cytopathological investigations and were found to be the cases of SIL (Squamous Intraepithelial Lesion) (90; 11.68%) and carcinoma cervix (4; 0.51%). The compatibility between histology and cytology was 100% in the 3 cases of the 4 cases of frank carcinoma cervix diagnosed on cytology. Study revealed greater age, higher parity, early marriage, poor educational status, rural habitation, sexually transmitted infections (mainly HPV; Human Papilloma Virus), clinical lesions of the cervix and ethnic groups variation as the predominant factors in the path of cervical carcinogenesis.Interpretations: Thus there is an urgent need for the initiation of community screening and educational programs through awareness campaigns along with the proposed suggestion for clinically down staging the disease by early stage detection.text/html2012-05-31T19:07:09+01:00http://www.webmedcentral.com/Dr. Brijesh SathianRisk Factors for the Development of Gastric Cancer, and their Awareness Among the General Public in Nepal: A Necessary Enquiry
http://www.webmedcentral.com/article_view/3429
Gastric carcinoma is a common malignancy in this part of world. There is need for follow up cohort studies regarding carcinogenic property of H. pylori and prevalence of its different strains in different ethnic groups in the sub-Himalayan belt. This may help in understanding the pathogenesis of gastritis and gastric cancer as well as the responsiveness and resistance of different anti-helicobacter regimens.The groups at highest risk include elderly males with history of alcoholism & smoked meat consumption from Gurung community and peoplewith history of smoking from Brahmin communities in Nepal. There is obvious scope of further studies on gastric carcinoma in other parts of this country and also to assess the other risk factors in this population. Nepal government has to gear up an awareness study and according to that an effective community based interventional programme.text/html2012-08-06T17:07:32+01:00http://www.webmedcentral.com/Dr. Zahid KhanAn Overview of Oral Cancer in Indian Subcontinent and Recommendations to Decrease its Incidence.
http://www.webmedcentral.com/article_view/3626
The Objective of this article is to review the current prevalence and risk factors for oral carcinoma across the Indian subcontinent. Oral cancer is increasing in Indian subcontinent mainly due to lack of hygiene, tobacco use, chewing tobacco leaves, smoking and many other factors which are discussed in detail in this article. Cancer is the second most common cause of mortality and morbidity today after cardiovascular problems. Oral cancer is the eleventh most common cancer in the world and two third deaths due to oral cancer occurs in developing world, out of which one third occurs in Indian Subcontinent. Human papilloma virus is a known risk factor oral cancer specially type 16 and 18. This is causing not only huge impact on the health of the community but also the economy of the Indian subcontinent countries. We have summarized few recommendations in this article, by which oral cancer can be tackled in Indian subcontinent. We have recommended different approaches from primary prevention to secondary and tertiary prevention methods. These include better hygiene, health education, and proper screening methods to detect those at risk, earlier treatment and smoking cessation clinics, proper legislation at government level and global approach as well.text/html2012-08-29T13:17:11+01:00http://www.webmedcentral.com/Dr. Hind El YacoubiPrimitive Heart Undifferenciated Sarcoma: A case Report and Literature Review
http://www.webmedcentral.com/article_view/3579
The primary malignant cardiac tumors are extremely rare, they represent 25% of all primitive cardiac tumors. We report a case of a man aged 45 years with a tumor of the left atrium, discovered by a dyspnea, hemoptysis and faintness, chest X-ray showed a cardiomegaly and pulmonary parenchymal overload. The echocardiography found a mass in the left atrium obstructing the mitral orifice at each diastole. A complete surgical resection was performed and pathological examination found an undifferentiated sarcoma, the patient was lost from view for 13 months. The reappearance of dyspnea related to local recurrence without metastasis has required a reoperation, immediate evolution was favorable. By the realisation of this observation, a literature review of the primary heart sarcoma was performed.text/html2012-09-06T17:35:48+01:00http://www.webmedcentral.com/Dr. Mohammed A BhatManagement of Intra-operative Tracheal Injuries during Trans-hiatal Esophagectomy for Carcinoma Esophagus
http://www.webmedcentral.com/article_view/3689
Tracheobronchial injury is a rare complication of transhiatal esophagogastrectomy, mostly seen in patients who receive neo-adjuvant therapy or have locally advanced growth with dense adhesions. Its’ immediate recognition and closure decreases the mortality and morbidity associated with this rare but fatal intra-operative complication. Retrospective analysis of 750 patients who underwent transhiatal esophagogastrectomy from, Jan 2002 to Jan 2012 for carcinoma esophagus was performed. Out of 608 patients who underwent transhiatal esophagogastrectomy, only four patients sustained injuries to major airways. Three injuries occurred during transhiatal and one injury during transcervical part of dissection. All the injuries occurred in trachea proximal to carina. All four injuries were closed primarily, re-enforced by muscle and fascial pledgets. In two patients the trachea was repaired through right thoracotomy and in two patients the cervical incision that was utilized for mobilization of esophagus in the neck provided adequate exposure for repair of the trachea.text/html2012-10-08T18:56:40+01:00http://www.webmedcentral.com/Prof. Wilson I OnuigboPostprostatectomy Urethral Stricture in Elderly Nigerians
http://www.webmedcentral.com/article_view/786
Purpose:We examined the outcome of urethral dilation in elderly patients of the Igbo ethnic group in Nigeria for stricture that supervened on radical prostatectomy.Methods:In this study, 10 men aged 65 years or older with proved urethral strictures underwent dilation. Their disease followed radical prostatectomy during the period from February, 1993 to December, 2005. The dilation was made under spinal (intrathecal) anesthesia.Results:In this patient cohort, we found that urethral dilation was undertaken without difficulty. Urine flow was stated to be good during follow up of up to 2 years.Conclusion: The predictive value of urethral dilation is such that it can be offered to elderly patients whose stricture resulted from prostatectomy.text/html2013-02-27T13:34:19+01:00http://www.webmedcentral.com/Dr. Ervin MingomatajSpontaneous Neoplasia: A Destiny of Viviparous Mammal
http://www.webmedcentral.com/article_view/4073
True cancers are more frequent among vertebrates, including viviparous mammals. The most evidenced risk factor for these pathologies among vertebrates seems to be retroviral infections. A part of their genome is incorporated mainly in mammalians as endogenous retroviruses (ERVs). This parasitic genome is vital for viviparous mammals, because functional ERVs are essential host system for transient immune suppression and tolerance of “foreign” embryo at the stage of trophoblast implantation. After that, the ERVs genome gets imprinted due to epigenetic mechanisms. In aging mammals, the ERVs genome could be epigenetically reactivated as an attempt to bypass the replicative cell senescence, leading also to the potential development of neoplasia. These facts may lead to the suggestion that ERVs genome is an evident risk factor per se in the development of spontaneous cancers among mammals. Generally, the development of cancer-like disorders among other phyla needs the stimulant effect of strong pollutants and the development of true cancer among other vertebrata needs the retroviral infections. In contrast to them, viviparous mammals contain the ERVs in their genome and therefore may develop the neoplasia even in absence of environmental oncogenic agents. This suggests that artificial exclusion of carcinogenic genome could be fatal for the viviparous mammalian self or at least for its natural reproduction, as long as ERVs genome is essential for transient immune suppression and tolerance of “foreign” mammalian embryo.text/html2013-03-25T13:31:55+01:00http://www.webmedcentral.com/Dr. Esther Una CidonPilot Study of Insomnia Prevalence in Cancer Survivors
http://www.webmedcentral.com/article_view/4161
The increasing number of cancer survivors forces professionals to deal with new symptoms such as insomnia or other sleep disturbances (SD). This study aimed to determine the prevalence and type of SD in a population of cancer survivors.
METHODS: Eligible patients treated with curative intent and followed a minimum of 4 years without recurrence. A cross sectional study was conducted over two months. Elegible patients if referred spontaneously insomnia. We collected socio-demographic, pathological and sleep related data.
RESULTS: 42 eligible. 54% conciliation insomnia followed by maintenance insomnia, early morning awakening and multiple awakenings.
Breast followed by colon cancer in women and gastrointestinal cancers followed by lung and prostate in men.
67% referred intrusive thoughts about cancer such as fear of relapse as the main cause. 57% referred morning fatigue and lack of enerfy.
CONCLUSIONS: A significant number of cancer survivors present insomnia mostly related to intrusive thoughts of fear to recurrence which impacts in his life due to fatigue and lack of energy. It would be important an early detection to establish the necessary measures for its control.text/html2013-04-22T17:35:02+01:00http://www.webmedcentral.com/Dr. Ervin MingomatajSpontaneous Neoplasia: A Destiny of Viviparous Mammal
http://www.webmedcentral.com/article_view/4212
True cancers are more frequent among vertebrates, including viviparous mammals. The most evidenced risk factor for these pathologies among vertebrates seems to be retroviral infections. A part of their genome is incorporated mainly in mammalians as endogenous retroviruses (ERVs). This parasitic genome is vital for viviparous mammals, because functional ERVs are essential host system for transient immune suppression and tolerance of “foreign” embryo at the stage of trophoblast implantation. After that, the ERVs genome gets imprinted due to epigenetic mechanisms. In aging mammals, the ERVs genome could be epigenetically reactivated as an attempt to bypass the replicative cell senescence, leading also to the potential development of neoplasia. These facts may lead to the suggestion that ERVs genome is an evident risk factor per se in the development of spontaneous cancers among mammals. Generally, the development of cancer-like disorders among other phyla needs the stimulant effect of strong pollutants and the development of true cancer among other vertebrata needs the retroviral infections. In contrast to them, viviparous mammals contain the ERVs in their genome and therefore may develop the neoplasia even in absence of environmental oncogenic agents. This suggests that artificial exclusion of carcinogenic genome could be fatal for the viviparous mammalian self or at least for its natural reproduction, as long as ERVs genome is essential for transient immune suppression and tolerance of “foreign” mammalian embryo.text/html2013-05-30T11:33:26+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroConsumption of the Dietary Flavonoids Quercetin, Luteolin and Kaempferol and Overall Risk of Cancer - A Review and Meta-Analysis of the Epidemiological Data
http://www.webmedcentral.com/article_view/4264
Numerous epidemiological and preclinical studies suggest that flavonoids may play an important role in the decreased risk of cancer associated with a diet rich in plant-derived foods. In this article, we have reviewed the epidemiological studies assessing the relationship between the consumption of three of the most common flavonoids, i.e. quercetin, luteolin and kaempferol, and the risk of developing cancer. We have also performed a meta-analysis on the consumption of these three flavonoids (alone and combined) and overall risk of cancer. The analysis of data from 18 case-control studies (8585 cases with cancer and 9975 control subjects) revealed that a high consumption of these three flavonoids (combined) was associated with a statistically significant reduction of overall cancer risk (OR: 0.73; 95% CI: 0.63, 0.84; p<0.01). A reduction of overall cancer risk was also observed for quercetin (OR: 0.73; 95% CI: 0.62, 0.86; p<0.01), kaempferol (OR: 0.86; 95% CI: 0.73, 1.11; p>0.05) and luteolin (OR: 0.90; 95% CI: 0.69, 1.18; p>0.05), which was statistically significant for quercetin. A high intake of these three flavonoids (combined) was also associated with a statistically significant reduction of lung cancer risk (OR: 0.67; 95% CI: 0.49, 0.91; p<0.05) and colon cancer risk (OR: 0.75; 95% CI: 0.57, 0.98; p<0.05). The analysis of data from 14 cohort studies (385033 individuals and 10809 cancer cases) showed a statistically significant reduction of overall cancer risk for the three flavonoids combined (RR: 0.89; 95% CI: 0.80, 1.00; p<0.05), for quercetin (RR: 0.82; 95% CI: 0.71, 0.96; p<0.05) and for kaempferol (RR: 0.88; 95% CI: 0.78, 0.99; p<0.05), and a non-statistically significant reduction for luteolin (RR: 0.95; 95% CI: 0.67, 1.34; p>0.05). These results suggest that consumption of foods rich in the flavonoids quercetin, kaempferol and luteolin may reduce the risk of developing cancer.
text/html2013-07-09T05:31:30+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroThe Cardiac Glycosides Digitoxin, Digoxin and Ouabain Induce a Potent Inhibition of Glycolysis in Lung Cancer Cells
http://www.webmedcentral.com/article_view/4323
Cardiac glycosides are promising anticancer drugs. We have recently shown that the cardiac glycosides digitoxin, digoxin and ouabain induce selective killing of lung cancer cells, and that the cytotoxicity of digitoxin against these cells occurs at concentrations below those observed in the plasma of cardiac patients treated with this drug (Oncogene, 2013. doi: 10.1038/onc.2013.229). Here we report that digitoxin, digoxin and ouabain induce a potent inhibition of glycolysis (glucose consumption and lactate production) in A549 cells at nanomolar concentrations. This inhibition was comparable to that observed with millimolar concentrations of the glycolysis inhibitor dichloroacetate, which is currently undergoing clinical trials for the treatment of cancer. Because platinum compounds are commonly used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with each cardiac glycoside; these combinations induced synergistic, antagonistic or additive effects mainly depending on the order at which the drugs were added to the cells.text/html2013-07-10T09:14:33+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroDichloroacetate, 2-Deoxyglucose and a Hydroalcoholic Extract from the Skin of the Fruit of Solanum melongena (Aubergine) Induce Selective Anticancer Activity against Melanoma Cells
http://www.webmedcentral.com/article_view/4326
Prognosis of melanoma patients with metastatic disease is very poor. For example, over 95% of melanoma patients with three or more sites of metastatic disease die within 1 year. Treatment failure usually occurs because the drugs used for the treatment of these patients have a low capacity to kill melanoma cells selectively. By using human UACC-62 melanoma cells and human VH-10 skin non-malignant cells, here we show that the glycolysis inhibitors dichloroacetate and 2-deoxyglucose, and an extract from the skin of the fruit of Solanum melongena (aubergine, eggplant), induce selective killing of melanoma cells. This selective anticancer activity was higher than that of the anticancer drugs etoposide, 5-fluorouracil, oxaliplatin and hydroxyurea. The glycolysis inhibitor 3-bromopyruvate did not show selective cytotoxicity towards the cancer cell line. We also report that UACC-62 melanoma cells have higher glycolytic rates (glucose consumption and lactate production) than VH-10 skin non-malignant cells, which may help explain the selective cytotoxicity of the glycolysis inhibitors dichloroacetate and 2-deoxyglucose towards the melanoma cell line. Since 2-deoxyglucose and dichloroacetate have already entered clinical trials for the treatment of specific cancers, our results support their possible advancement into clinical trials for the treatment melanoma patients with metastatic disease. The selective anticancer activity of the extract from the aubergine skin warrants further investigation.text/html2013-07-12T06:30:28+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroVitamin C and the Red Wine Polyphenol Resveratrol - but not Curcumin and the Glycolysis Inhibitors 2-Deoxyglucose, Dichloroacetate and 3-Bromopyruvate - Induce Selective Cytotoxicity against Lung Cancer Cells
http://www.webmedcentral.com/article_view/4329
Cancer statistics show that the most commonly diagnosed cancer in the world is lung cancer, that over 50% of patients diagnosed with this cancer have distant metastasis, and that only 4% of these patients manage to survive more than 5 years. The limited selective cytotoxicity of the drugs used for the treatment of these patients probably accounts for these high mortality rates. In this work, we have assessed the selective anticancer activity of several drugs currently undergoing clinical trials by using human A549 lung cancer cells and human MRC5 non-malignant lung fibroblasts. Vitamin C and the red wine polyphenol resveratrol induced selective cytotoxicity towards the cancer cell line. Vitamin C (1 mM) induced higher selective cytotoxicity than the anticancer agents cisplatin, oxaliplatin, etoposide and 5-fluorouracil. A lyophilized red wine extract, but not a hydroalcoholic extract from red grapes, also showed certain selectivity against lung cancer cells. Neither the curry polyphenol curcumin nor the glycolysis inhibitors 2-deoxyglucose, dichloroacetate and 3-bromopyruvate displayed selective cytotoxicity. We also report that A549 lung cancer cells have higher glycolytic rates (higher glucose consumption and higher lactate production) than human MRC5 non-malignant lung fibroblasts, and that the combination of each glycolytic inhibitor with the pro-oxidant agents pyrogallol and hydrogen peroxide does not result in a significant increase in their cytotoxicity or selectivity against the cancer cell line. Our results support the possible evaluation of vitamin C and resveratrol in clinical trial for the treatment of metastatic lung cancers, and suggest that curcumin and the glycolysis inhibitors 2-deoxyglucose, dichloroacetate and 3-bromopyruvate have a limited potential (at least as single agents) for the treatment of patients with this type of cancer.text/html2014-02-03T05:30:05+01:00http://www.webmedcentral.com/Dr. Esther Una CidonAn Oncology Nursing Intervention to Reduce Adverse Drug Events in Ambulatory Cancer Patients
http://www.webmedcentral.com/article_view/4535
Objective: To increase cancer patients safety in our Day Oncology Care Unit (DOCU).
Methods: We conducted a retrospective review of records to determine the most frequent causes of Adverse Drugs Events (ADEs) and the time it took to detect and treat them. We then provided nursing education to instruct oncology nurses on how to address and prevent ADEs.
Results: After the implementation of this project, the incidence of ADEs has been as it has been the time invested in addressing those complications correctly.
Conclusion: Nursing staff education at a DOCU has improved patient’s safety and reduced ADEs. text/html2014-02-07T11:22:44+01:00http://www.webmedcentral.com/Dr. Esther Una CidonA rare cause of melanonychia
http://www.webmedcentral.com/article_view/4542
Melanonychia is a rare side effect with an unknown etiology mechanism. It is believed that this side effect derives from a damage in the nail bed or matrix, focal stimulation of nail-matrix melanocytes and photosensitization. Many cases secondary to hydroxiurea have been described, though there have been also cases with nail hyperpigmentation secondary to cyclophosphamide or doxorubicin but neither of them complicated with black nails as we show here.text/html2015-05-01T14:13:29+01:00http://www.webmedcentral.com/Dr. Miguel Lopez-LazaroEffect of DNA repair deficiencies on the cytotoxicity of resveratrol
http://www.webmedcentral.com/article_view/4885
Numerous preclinical studies have shown that the naturally-occurring polyphenol resveratrol may produce health-beneficial effects in a variety of disorders, including cancer, diabetes, Alzheimer, and cardiovascular diseases. Resveratrol has entered clinical trials for the prevention and treatment of several of these disorders. This polyphenol is also available in the market as a dietary supplement. Experimental data have shown, however, that resveratrol induces DNA damage in a variety of cells. Here we review such evidence and evaluate the cytotoxicity of resveratrol (MTT assay) in cells deficient in several major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, and Fanconi anemia repair). Cells deficient in base excision repair (EM9), nucleotide excision repair (UV4 and UV5) and Fanconi Anemia (KO40) were slightly hypersensitive to resveratrol-induced cytotoxicity with respect to their parental cells (AA8). Our results suggest that these pathways may participate in the repair of the DNA damage induced by resveratrol and that deficiencies in these pathways may confer hypersensitivity to the genotoxic activity of this dietary constituent. text/html2015-06-08T15:54:04+01:00http://www.webmedcentral.com/Ms. Sneha BalaniUnderstanding Triple Negative Breast Cancer
http://www.webmedcentral.com/article_view/4895
Triple Negative Breast Cancers (TNBCs) are distinct breast malignancies that are characterized by the lack of clinically relevant expression of estrogen-, progesterone- receptors (ER/PR) and HER2/neu proteins. With a molecular profile similar to the basal-like carcinomas, the aggressive behavior of TNBCs is orchestrated with a display of distinct metastasis patterns. In absence of targeted therapies they rapidly transform into the most dreaded cancers affecting various parts of the body, with usually worst prognosis. Majority of BRCA1 associated breast cancers are triple negative, but the extent of BRCA1’s involvement is still under investigation. Epidemiologically, TNBCs are prevalent among young African-American women, who display a unique risk factor profile, are characterized by distinct recurrence patterns and a redilection for brain metastasis. Clinical trials for chemicals agents targeting epidermal growth factor receptor (EGFR) and inhibitors of poly ADP-ribose polymerase (PARP) hold the promise in the treatment of TNBC.text/html2017-04-03T08:46:01+01:00http://www.webmedcentral.com/Dr. Deepak GuptaWater or Wipe: Implications for Human Papilloma Virus Associated Cancers?
http://www.webmedcentral.com/article_view/5266
It's commendable statistic that was deciphered by Islami et al (2016). It is interesting question raised by them whether the trends of receptive anal intercourse may explain the trends towards anal cancer incidence among various countries. However, they could have also reflected in their discussions whether plain water vs. dry wipe role in anal hygiene could potentially contribute to the trends in anal cancer because it would be worth a while to investigate whether post-defecation water use with associated anogenital hygiene variability in itself can act as an independent shield in our battle against anogenital cancer.text/html2018-02-02T05:04:16+01:00http://www.webmedcentral.com/Dr. Esther Una CidonChemotherapy induced oral mucositis: prevention is possible
http://www.webmedcentral.com/article_view/5433
Oral mucositis (OM) is a frequent side-effect of antineoplastic treatments. Patients usually describe the first symptom as burning sensation in the mouth and swelling, erythema or ulceration and pain will follow.
These will place them at a higher risk of infection, might impair significantly their nutritional status and worsen their quality of life. Consequently, OM might lead to noncompliance with the oncological treatment with a negative impact on survival. Numerous treatments have been used to alleviate OM and improve patient’s nutritional status, but so far, no definite therapy has demonstrated the ability to prevent it.
We have recently published a prospective study in patients with breast cancer undergoing treatment with neoadjuvant or adjuvant intent. Patients received either FEC (5 fluorouracil, epirubicin and cyclophosphamide) or Docetaxel. Our results showed a significant reduction in the rate of OM grade 2–3 with a especial mouthwash containing steroids, antifungal and saline. Patients were instructed on the correct use based on the chronology and duration of the previous episode of OM. Although further evaluation is warranted, we have been widely using this especial mouthwash in our patients.
We present here the case of a male diagnosed with colorectal cancer, who has been receiving palliative treatment with FOLFOX and Panitumumab. He struggled with OM after the first cycle and after using the special mouthwash, he found a significant benefit with the following treatments. text/html2018-02-12T06:55:49+01:00http://www.webmedcentral.com/Dr. Esther Una CidonGemcitabine-induced haemolytic uremic syndrome: high level of suspicion seems crucial
http://www.webmedcentral.com/article_view/5437
Dear editor,
Gemcitabine is an antimetabolite agent used in the treatment of many tumours. The safety profile of gemcitabine is generally mild and it usually displays minimal toxicity in elderly too. Furthermore, its profile of side-effects does not seem to be related to patient’s age.
There is no evidence of cumulative renal or hepatic toxicity and peripheral oedema has not been related to any cardiac, hepatic or renal dysfunction. Unfortunately, it has got its negative side as well. Although infrequent, haemolytic uremic syndrome (HUS) can be induced by this treatment. The incidence seems to be low, although underreporting could also be a possibility.
It has been published that around 0.078% patients in clinical trials, or 0.008% reported from daily clinic, developed HUS. This places the overall incidence at 0.015%1,2. However, the mortality rate of these cases ranges from 10 to 40% in most series, but it could be as high as 70% in others3,4.
This could be partly due to many cases included having disseminated disease, which make more difficult to know the cause of the HUS (underlying neoplasia or Gemcitabine)5.
Several authors have suggested that cancer associated HUS usually happens when the disease has already disseminated, whereas Gemcitabine-associated HUS is more frequent in patients under adjuvant treatment5.
In any case, this complication is underdiagnosed and this could be due to myelosuppression related to chemotherapy, poor oral intake or diarrhoea, especially in those patients who suffer from pancreatic insufficiency after Whipple’s procedure and find difficult to find the correct personalised dose of pancreatic enzimes, or those having other comorbidities such as hypertension, vascular disease, diabetes, etc.
A high index of suspicion is necessary and should be applied when patients develop renal insufficiency in the presence of myelosuppression. This should prompt a laboratory workup looking for hemolysis and microangiopathy signs. High levels of LDH, low levels of haptoglobin, increased reticulocyte count, a peripheral blood smear showing fragmented red blood cells, schistocytes, will help differentiate renal insufficiency associated to myelotoxicity or HUS. Moreover, a mild renal impairment will resolve quickly on rehydration or treatment of the underlying prerenal cause.
In addition, the Coombs' test should be negative if myelosuppression.
We have had two cases of Gemcitabine-induced HUS and both of them continue on hemodyalisis. These two patients were receiving adjuvant Gemcitabine and both showed a significant drop in haemoglobin levels, from baseline, after commencing cycle 5 and at the same time, a significant drop in creatinine clearance. One of them did not finish cycle 6 but the other completed the 6 planned cycles.
We reviewed a total of 157 patients who had received adjuvant Gemcitabine for pancreatic carcinoma. We collected all data about haemoglobin, platelets, white cells count, creatinine clearance before each cycle of Gemcitabine. We calculated the maximum drop between baseline and minimum level of haemoglobin and creatinine clearance for all these patients. We found that all patients, except the two who developed HUS, had a maximum drop in haemoglobin of around 24% (22-27%) and around 17% in creatinine clearance (12-44%). Those two patients had a drop in haemoglobin of 37% and 34% and a drop in creatinine clearance of 41% and 31%.
Logistic regression analysis showed that a drop in haemoglobin >25% and in creatinine clearance >30% from baseline, increased significantly the chances of ending on hemodyalisis (p 0.0001).
The patient who had a significant drop in renal function and recovered, showed at the same time a very mild drop in haemoglobin and other signs of myelotoxicity (low white cells count).text/html2019-04-25T06:44:46+01:00http://www.webmedcentral.com/Dr. Esther Una CidonTriple-Negative Breast Cancer: a brief overview.
http://www.webmedcentral.com/article_view/5563
Background
Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 15-20% of all breast cancers. This represents the most challenging molecular subtype of breast cancer.
Methods
This article will make a comprehensive review of these therapies in the treatment of TNBC and it will give a glimpse into the near future of this difficult disease.
Results
Currently, chemotherapy is the standard treatment but active research tries to find actionable targets or other molecules to treat this aggressive disease with higher levels of success.
Immunotherapy has emerged as an attractive therapy in various cancers including this disease but other agents deserve our attention as well. Among these agents, the poly-ADP-ribose polymerase (PARP) inhibitors, platinum-based drugs, anti-epidermal growth factor receptor (EGFR) inhibitors, and anti-vascular endothelial growth factor receptor (VEGF) inhibitors are the most relevant ones.
Conclusion
Current treatment options for these patients are restricted to chemotherapy. However, research continues to advance and hopefully soon, other agents could be approved and use as standard approaches to this difficult disease. text/html2019-09-19T07:15:40+01:00http://www.webmedcentral.com/Dr. Esther Una CidonScalp cooling use in breast cancer patients receiving neoadjuvant/adjuvant systemic chemotherapy in England
http://www.webmedcentral.com/article_view/5592
Background
Chemotherapy-induced alopecia is a distressing side-effect. Currently the use of scalp cooling has been encouraged but we do not really know the rate of compliance or success in routine practice.
Methods
We have carried out an audit in our centre to assess both, compliance and success in our patients diagnosed with breast cancer who will start chemotherapy with neoadjuvant or adjuvant intent. The degree of hair loss was assessed before cycle 2 and the last cycle, using Dean’s scale.
Results
72 patients were assessed. 27.7% decided to use the scalp cooling, many declined, most of them (61.5%) argued that they were not worried about hair loss. Dean's alopecia score was excellent in 25%, good in 10%, and moderate/poor in 65%.
Conclusions
Although scalp cooling may prevent significant alopecia, our patients continue to be reluctant arguing that hair loss does not bother them much. Perhaps the fear of scalp metastases or the reduced benefit from chemotherapy, recognised by patients in forums but not with doctors, need a frank conversation and further education.text/html2022-08-08T01:56:47+01:00http://www.webmedcentral.com/Dr. Esther Una CidonAudit of Paclitaxel induced Peripheral Neuropathy in Early Breast Cancer
http://www.webmedcentral.com/article_view/5788
Paclitaxel induced peripheral neuropathy (PIPN) is predominantly sensory. It usually appears with higher cumulative doses (>1,400 mg/m2), being less frequent with weekly regimens or lower doses.
Numbness, paresthesias and burning pain in a glove-and-stocking distribution, distal and symmetrical are the most frequent symptoms. Although mild symptoms tend to improve or resolve within months after cessation of paclitaxel, more intense symptoms may last for longer or even persist.
PIPN risk factors have been researched for a long while but findings are still inconclusive.
In this scenario, we carried out an audit on a small cohort of patients diagnosed with early breast cancer, receiving weekly paclitaxel as part of their adjuvant or neoadjuvant regimen of chemotherapy with the aim of knowing the incidence of peripheral neuropathy, the intensity of symptoms, and the role of several potential risk factores on the appearance of PIPN. text/html2023-07-10T03:19:34+01:00http://www.webmedcentral.com/Dr. Esther Una CidonA short review of results with palbociclib in a real world daily clinic
http://www.webmedcentral.com/article_view/5826
Background: Palbociclib (P) was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved for ER+/HER-2 negative advanced breast cancer patients. Neutropenia is commonly observed.
Aim: We carried out a review of our data to provide a real-world experience of the results and toxicities associated with this therapy in our population of patients.
Patients and methods: Retrospective review of ER positive metastatic breast cancer patients treated with Palbociclib at the University Hospital Dorset.
Results: 64 women included. All had received P in combination either with L (46) or F (18). Median age 63 years old (36-84). 30 patients (46.8%) required dose adjustments, with 19 of them (63.6%) requiring this during the first 3 months of treatment (early dose adjustment). 9 patients (out of 64, 154.06%) required a second dose adjustment. No discontinuation due to toxicities. Adverse events as expected; only one case of repeated thromboembolic events was reported.
At the time of collecting these data, with a m follow up of 33 months, the mPFS was 26 months with P + L and 15m with P + F. And mOS was not reached in any of the combinations.
36 patients were alive with P+L (78.2%) and 10 had died (21.7%). With P+F, 12 were alive (66.7%) and 6 (33.3%) had died.
32 patients had progressed at the time of data cut-off. 13 with P+F and 19 with P+L.
Conclusion: Although we will continue to follow these patients to get final conclusions, our data are in line with other real life studies showing benefits with these combinations with expected toxicities.