Search

Background: Colon cancer generally begins as a neoplastic growth of tissue, called polyps, originating from the inner lining of the colon wall. Most colon polyps are considered harmless but over the time, they can evolve into colon cancer, which, when diagnosed in later stages, is often fatal. Hence, time is of the essence in the early detection of polyps and the prevention of colon cancer. Methods: To aid this endeavor, many computer-aided methods have been developed, which use a wide array of techniques to detect, localize and segment polyps from CT Colonography images. In this paper, a comprehensive state-of-the-art method is proposed and categorize this work broadly using the available classification techniques using Machine Learning and Deep Learning. Conclusions: The performance of each of the proposed approach is analyzed with existing methods and also how they can be used to tackle the timely and accurate detection of colon polyps.

Express MS identification of biological tissues has become a much more accessible research method due to the application of direct specimen ionization at atmospheric pressure. In contrast to traditional methods of analysis employing GC-MS methods for determining the molecular composition of the analyzed objects it eliminates the influence of mutual ion suppression. Despite significant progress in the field of direct MS of biological tissues, the question of mass spectrometric profile attribution to a certain type of tissue still remains open. The use of modern machine learning methods and protocols (e.g., "random forests") enables us to trace possible relationships between the components of the sample MS profile and the result of brain tumor tissue classification (astrocytoma or glioblastoma). It has been shown that the most pronounced differences in the mass spectrometric profiles of these tumors are due to their lipid composition. Detection of statistically significant differences in lipid profiles of astrocytoma and glioblastoma may be used to perform an express test during surgery and inform the neurosurgeon what type of malignant tissue he is working with. The ability to accurately determine the boundaries of the neoplastic growth significantly improves the quality of both surgical intervention and postoperative rehabilitation, as well as the duration and quality of life of patients.Ékspress-identifikatsiia biologicheskikh tkaneĭ stala sushchestvenno bolee dostupnym metodom issledovaniia blagodaria primeneniiu metodov mass-spektrometrii s priamoĭ atmosfernoĭ ionizatsieĭ. V otlichie ot traditsionnykh metodov analiza, ispol'zuiushchikh khromato-mass-spektrometricheskie metody opredeleniia molekuliarnykh komponent issleduemykh ob"ektov, ona iskliuchaet vozmozhnost' ucheta éffektov podavleniia razlichnymi ionami drug druga po rezul'tatam izmereniĭ. Nesmotria na sushchestvennyĭ progress v oblasti priamoĭ mass-spektrometrii biologicheskikh tkaneĭ, vopros atributsii mass-spektrometricheskogo profilia opredelennomu vidu tkani ostaetsia otkrytym. Primenenie sovremennykh metodov mashinnogo obucheniia (sluchaĭnykh lesov) pozvoliaet prosledit' vzaimosviaz' mezhdu komponentami mass-spektrometricheskogo profilia i rezul'tatom identifikatsii tkani opukholi mozga (astrotsitomy ili glioblastomy). V dannoĭ rabote pokazano, chto osnovnye otlichiia v mass-spektrometricheskikh profiliakh étikh opukholeĭ obuslovleny ikh lipidnym sostavom. Poluchenie statisticheski dostovernykh razlichiĭ lipidnykh profileĭ astrotsitomy i glioblastomy pozvoliaet bystro provodit' analiz vo vremia khirurgicheskoĭ operatsii i soobshchat' neĭrokhirurgu, s kakoĭ tkan'iu on rabotaet. Vozmozhnost' tochnogo opredeleniia granits novoobrazovaniia sushchestvenno uluchshaet kachestvo i operativnogo vmeshatel'stva, i postoperatsionnoĭ reabilitatsii, ravno kak i prodolzhitel'nost' i kachestvo zhizni patsientov.

This minireview presents the contribution of estrogens and other hormones to the etiopathogenesis of tumors, as well as to the phenomena of perinatal programming/imprinting for various types of cancer. In addition, the importance of endocrine disruptors is discussed in the ontopathogeny of some oncologic diseases. The important role of stress and glucocorticoids, as referred to neoplastic growth, is highlighted. It is proposed that greater attention should be paid to the maintenance of the balance between cellular proliferation, the survival capacity of cells, and apoptosis as the basis for the bioregulation of normal and pathologic growth.

Resveratrol (RV) is a polyphenol nonflavonoid compound present in strongly pigmented vegetables and fresh fruits as well as dried nuts such as peanuts. High concentrations of this natural compound were found in the modern Western world in the peel of the red grape (Vitis vinifera) but usage of this natural drug in popular medicine was documented much earlier. RV exhibits diverse biological activities such as antitumor, antioxidant, antiviral, and phytoestrogenic, but at high concentrations RV may show cytotoxic effects. Other natural substances behave in a similar way, such as curcumin and a semipurified fraction of the whole neem oil. The bioproperties of these natural products are also discussed. Administration of RV to cultured cells alters the permeability and fluidity of the cell membrane. The literature ascribes to RV an antiproliferative action which renders it a good candidate for the control of neoplastic growth. The authors also examine the possibility of using nanoparticles as potential vehicles for drug (RV) delivery. This specific topic is rapidly expanding and results referring to the action of carbon nanotubes and graphene sheets are also illustrated. A brief overview of other bioactive substances and potential candidates for nano-delivery is also discussed.

SUMMARYAggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.

Portal vein thrombosis in patients with liver cirrhosis may be due neoplastic growth invading portal vein or due to non-neoplastic causes. The indications for treating PVT in cirrhotic individuals are diffi cult to be established but at least are of great benefi t in acute PVT. Investigating the cause of portal vein thrombosis in cirrhotic patient prepared for splenectomy including virology and immune markers, AFP, triphasic CT. Factor V Leiden mutation and prothrombin gene 20210. The case showed non-neoplastic portal vein thrombosis due to portal pyemia with underlying prothrombin gene 20210 polymorphism. The early initiation of anticoagulation after the diagnosis of acute PVT may be the only predictive factor for complete PV recanalization with preservation of liver function.

Deep benign fibrous histiocytoma (DBFH) is a rare mesenchymal tumor compared with cutaneous fibrous histiocytoma. As the diagnosis of DBFH may be clinically difficult, the presence of DBFH is usually confirmed after its excision. In this case study, we report a case of a 31-year-old man who lived with a painless mass in his right thigh for 15 years. After its examination by preoperative ultrasound and magnetic resonance imaging, the tumor was completely excised. Further histologic evaluation revealed neoplastic growth composed of proliferating spindle cells forming short fascicles and a storiform pattern. The patient was diagnosed with DBFH on the basis of its intraoperative, radiologic, and histopathologic features. Keywords: Benign fibrous histiocytoma, Soft tissue tumor, DBFH subcutaneous, Thigh

Radiotherapy is still a treatment of choice for many malignancies, often in combination with other strategies. However, its efficacy is limited by the dose that can be safely administered without eliciting serious side-effects, as well as the fact that recurrence is common, particularly in large tumours. Combining radiotherapy with drugs that could sensitise cells to radiation and/or reduce the factors that promote the recovery of the surviving cancer cells is a promising approach. Ionising radiation has been shown to induce senescence and the accumulation of senescent cells creates a microenvironment that facilitates neoplastic growth. This provides a rationale to test the addition of anti-senescent drugs, some of which are already available in the clinic, to radiotherapy protocols. Here, we discuss the relevance of radiotherapy-induced senescent cell accumulation and the potential interventions to minimise its negative effects.

Upper urinary tract urothelial carcinoma (UTUC) can be defined as any neoplastic growth that affects the lining of the urinary tract from the renal calyces to the distal ureter. UTUC has similar behaviors to urothelial cell carcinoma in bladder (UBC), but prognosis and tumor characteristics are different. However, UTUC is known as a relatively rare disease and has poor prognosis than UBC.

Mandibular accessory condyle is rare. Literature search found most of the accessory condyles to arise from the mandibular coronoid process due to hyperactivity of attached temporalis muscle. Although neoplastic growth at mandibular coronoid mimicking an accessory condyle also been cited. Absence of report in recent publications regarding accessory mandibular condyle arising from the main mandibular condyle makes this anomali extremely rare. The present case report is about a true accessory mandibular condyle which caused the patient facial and occlusal disharmony. A 3D computerized tomographic imaging ascertained the exact location of the accessory condyle, its origin and resting position of the accessory and the main condylar head. The facial and occlusal disharmony settled completely within a short postoperative time following surgical intervention and mild elastic traction.Delta Med Col J. Jan 2016 4(1): 45-50

Pseudomyxoma peritonei (PMP) is a rare disease with neoplastic growth of mucin-secreting cells in the peritoneal cavity, resulting in mucinous ascites. The septum of intra-abdominal fluid collection is a key imaging finding characteristic to PMP. In magnetic resonance imaging (MRI), multi-b value diffusion-weighted imaging (DWI) is a method used to obtain an accurate apparent diffusion coefficient. The clinical utilities of DWI using lower b values as diagnostic imaging are rarely highlighted. This report describes a case of PMP in which DWI using b values of 100 and 500 s/mm(2) exclusively visualized many thick septa with low signal intensity in peritoneal effusion. The septa could not be recognized in DWIs with b values of zero or 1000 s/mm(2), as with ultrasonography, computed tomography, and conventional MRI. A discrepancy between DWI using lower b values and other MRI sequences or imaging modalities indicates a specific capability of DWI using low b values: the ability to visualize septa of intra-abdominal fluid collection much thicker than in real cases. Results for this case suggest that DWI using low b values might present clinical potential for the preoperative diagnosis of PMP.

Mitochondria are dynamic organelles that exchange a multiplicity of signals with other cell compartments, in order to finely adjust key biological routines to the fluctuating metabolic needs of the cell. During neoplastic transformation, cells must provide an adequate supply of the anabolic building blocks required to meet a relentless proliferation pressure. This can occur in conditions of inconstant blood perfusion leading to variations in oxygen and nutrient levels. Mitochondria afford the bioenergetic plasticity that allows tumor cells to adapt and thrive in this ever changing and often unfavorable environment. Here we analyse how mitochondria orchestrate the profound metabolic rewiring required for neoplastic growth.

Background Perivascular epithelioid cell tumors (PEComa) are exceedingly rare mesenchymal neoplasms arising in a variety of anatomic sites. mTOR inhibitors are active in these neoplasms. However, no other effective treatments are available in those patients progressing to them. The PI3K–Akt–mTOR signaling pathway modulates neoplastic growth through signaling activation of ER and the EGF receptor family of receptor tyrosine kinases. ER drives PI3K/AKT activation in response to mTORC1 inhibition. This provides a rationale for combining anti-estrogens and mTORC1 inhibitors. Methods We retrospectively identified patients with advanced PEComa treated with mTOR inhibitors since January 2002 at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan – Italy. In a subgroup of them, exemestane was added at the time of progression. Results Twenty-eight patients with advanced PEComa treated with mTOR inhibitors were identified. Twenty–six were evaluable for response. Twelve out 26 (46%) had a PR and seven (27%) a SD, with a median PFS of 7 months. At the time of progression to sirolimus, 5 patients received a combination of sirolimus and exemestane and one of sirolimus, exemestane and GnRH. Three patients out 6 had a PR, 2 out 6 had a SD, and 1 out 6 had a PD, with a median PFS of 6 months. In this subgroup of patients treated with the combination, previous PFS to mTOR inhibitors was 6.6 months. Conclusions In this small retrospective series, the combination of mTOR inhibitors and exemestane obtained a reversion of resistance to mTOR inhibitors in one half of patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure R. Sanfilippo: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Advanchen Laboratories; Research grant / Funding (institution): Amgen Dompe; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Epizyme Inc; Research grant / Funding (institution): Galxo; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. C. Fabbroni: Research grant / Funding (institution): Advanchen Laboratories; Research grant / Funding (institution): Amgen Dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Epizyme Inc; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): PharmaMar. E. Fumagalli: Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): karyopharm Pharmaceuticals; Research grant / Funding (institution): Pfizer. R. Bertulli: Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo ; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): PharmaMar. S. Stacchiotti: Research grant / Funding (institution): Karyopharm Pharmaceuticals; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Advenche Laboratories; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Pfizer. P.G. Casali: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Deciphera; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Advenchen Laboratories; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Blueprint Midicines; Research grant / Funding (institution): AROG Pharmaceuticals; Research grant / Funding (institution): Amgen dompe’; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Epizyme; Research grant / Funding (institution): Glaxo; Research grant / Funding (institution): KaryopharmPharmaceuticals; Research grant / Funding (institution): PharmaMar. All other authors have declared no conflicts of interest.

Graft-versus-host disease-associated angiomatosis (GVHD-AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor-derived endothelial cells within areas of GVHD-AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.

The temporomandibular joint (TMJ) is decisive for normal jaw function such as chewing, swallowing, speaking, oral health, and nutrition. Temporomandibular disorders (TMDs) refer to a group of disorders affecting the TMJ, masticatory muscles, and the associated structures. TMDs are considered as a multifactorial disorder. These conditions have been unable to reveal a common etiology or biological basis in terms of apparent signs and symptoms, and hence considered a heterogeneous group of health problems associated with chronic pain. These disorders share the symptoms of pain, limited mouth opening, and joint noises. The causes of TMDs range from traumatic injury to immune-mediated systemic disease to neoplastic growth to incompletely understood neurobiological mechanisms. This article presents an overview of the various etiological factors, signs, and symptoms related to TMDs.

Cervical cancer is the most common gynecological malignancy in the developing countries like India. In addition to human papillomavirus (HPV) infection, host genetic factors play an important role in viral persistence and neoplastic growth. IL-10, a multifunctional cytokine, plays an active role to promote tumor growth in the presence of HPV. The present study aims to find out the impact of IL-10 promoter polymorphisms at -1082A/G (rs1800896), -819C/T (rs1800872), and -592C/A (rs1800871) sites along with IL-10 production and HPV infection in the progression of cervical cancer. We have genotyped a total of 506 subjects, 256 cases (208 cervical cancer + 48 precancer), and 250 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method followed by sequencing. IL-10 serum concentration was measured by enzyme-linked immunosorbent assay. The frequency of IL-10 -592 variant genotype (AA) was found significantly reduced in cases as compare to controls while -1082 variant genotype (GG) was found ~4-fold higher risk of cervical cancer (p =

The overwhelming majority of the pituitary tumours are benign adenomas that remain a serious challenge to endocrinologists and neurosurgeons by virtue of great variety of their early manifestations, the impossibility to predict the neoplastic growth, and the influence exerted on the patients' quality of life. Most pituitary adenomas are sporadic tumours and only few of them develop in the framework of hereditary syndromes. The present review is focused on the variants of hereditary syndromes with special reference to various pituitary neoplasms. The molecular and genetic studies revealed several genetic defects that are believed to contribute to the formation of pituitary adenomas. Moreover, a few genes were identified responsible for the development of hereditary forms of pituitary tumours. Identification of such genes and pathogenetic mechanisms underlying the development of pituitary microadenomas is of paramount importance for the improvement of their diagnostics and treatment that in its turn may promote the understanding of pathogenesis of sporadic adenomas and improve their prognosis.

Angiogenesis is the basis for neoplastic growth in human tissues. Nevertheless, neovascularization may be present both in benign and malignant lesions. Although microvascular density assessment is a useful tool for the study of neoplastic vascularization, it cannot be used on a large scale because of the invasiveness of the method. When contrast-enhanced ultrasonography (CEUS) was introduced in clinical practice, the initial results in the field of breast lesions were disappointing because differentiation between benign and malignant masses was not possible. Magnetic resonance imaging (MRI) assessment of the microvascular features was therefore immediately accepted because of the higher diagnostic accuracy. However, in the last decade the sensitivity and specificity of CEUS have greatly improved due to the development of more sophisticated ultrasound (US) equipment, the introduction of second-generation contrast agents and the development of dedicated software able to perform quantitative analysis. This literature review compares the main results reported in the literature regarding the use of CEUS for the characterization of neoplastic lesions of the breast. All the authors agreed that malignant lesions show early wash-in with more intense enhancement and fast wash-out in comparison with benign masses. However, there is still no observer agreement regarding vascularization patterns, and different classifications are proposed. The conclusion of this literature review is therefore that the clinical role of CEUS in the diagnostic process and in follow-up is still to be clearly defined.Die Angiogenese ist die Ursache für neoplastische Wucherungen im humanen Gewebe. Doch die Gefäßneubildung kann sowohl bei gutartigen als auch in malignen Herdbefunden auftreten. Obwohl die Bestimmung der mikrovaskulären Dichte ein nützliches Mittel für die Untersuchung der neoplastischen Gefäßneubildung ist, kann diese invasive Methode nicht in größerem Maßstab eingesetzt werden. Mit Einführung der kontrastverstärkten Sonografie (CEUS) in die klinische Praxis waren die ersten Ergebnisse auf dem Gebiet der Herdbefunde der Brust enttäuschend, da eine Unterscheidung zwischen gutartigen und malignen Raumforderungen nicht möglich war. Wegen der höheren diagnostischen Genauigkeit wurde die Bestimmung der mikrovasalen Merkmale durch Magnetresonanz-Tomografie (MRT) sofort anerkannt. Im letzten Jahrzehnt haben sich jedoch die Sensitivität und Spezifität der CEUS durch die Entwicklung einer technisch ausgereiften Ultraschall(US)-Ausstattung, durch die Einführung von Kontrastmitteln der zweiten Generation und durch den Aufbau einer geeigneten Software für die quantitative Analyse deutlich verbessert. Dieser Literaturüberblick vergleicht die publizierten wichtigsten Ergebnisse zur Anwendung von CEUS bei der Charakterisierung neoplastischer Herdbefunde der Brust. Alle Autoren stimmen darin überein, dass maligne Herdbefunde im Vergleich zu gutartigen Raumforderungen einen frühes Wash-in und eine etwas deutlichere Verstärkung sowie eine schnelles Wash-out zeigen. Dennoch gibt es noch keine Übereinstimmung der Beobachter, was die Vaskularisierungsmuster anbelangt, und verschiedene Klassifizierungen werden vorgeschlagen. Deshalb kommt diese Übersicht zu dem Fazit, dass der klinische Stellenwert von CEUS für die Diagnosestellung und Nachsorge noch eindeutiger definiert werden muss.

The response of the immune system to neoplastic growth can be a key determinant in the course of neoplastic disease. While chronic inflammation has been implicated as a potential cause of some neoplastic growth, it is also clear that the immune system can control and even eliminate it as well. Harnessing this interaction has become an intense focus of anti-cancer research with the development of tumour vaccines and immune modulating therapies. While this interaction is inherently dynamic and complex, the diagnostic pathologist is given a static snapshot of the tumour–immune system interface that can have useful information for treating clinicians. Cancer-associated lymphocytic inflammation, or tumour-infiltrating lymphocytes (TILs), appear to have prognostic and predictive relevance in a variety of neoplasms. Accurate quantification of TILs has become a recommended reporting element for malignancies like melanoma, Merkel cell carcinoma and colon cancer. In this review, we will discuss the current understanding of tumour-infiltrating lymphocytes and their subsets in a variety of cancers, as well as recommendations for reporting of tumour-infiltrating lymphocytes in cancer.

Neoplastic growth and cellular differentiation are critical hallmarks of tumor development. It is well established that cell-to-cell communication between tumor cells and “normal” surrounding cells regulates tumor differentiation and proliferation, aggressiveness, and resistance to treatment. Nevertheless, the mechanisms that result in tumor growth and spread as well as the adaptation of healthy surrounding cells to the tumor environment are poorly understood. A major component of these communication systems is composed of connexin (Cx)-containing channels including gap junctions (GJs), tunneling nanotubes (TNTs), and hemichannels (HCs). There are hundreds of reports about the role of Cx-containing channels in the pathogenesis of cancer, and most of them demonstrate a downregulation of these proteins. Nonetheless, new data demonstrate that a localized communication via Cx-containing GJs, HCs, and TNTs plays a key role in tumor growth, differentiation, and resistance to therapies. Moreover, the type and downstream effects of signals communicated between the different populations of tumor cells are still unknown. However, new approaches such as artificial intelligence (AI) and machine learning (ML) could provide new insights into these signals communicated between connected cells. We propose that the identification and characterization of these new communication systems and their associated signaling could provide new targets to prevent or reduce the devastating consequences of cancer.

Tissue-specific stem cells are responsible for the maintenance of the epithelium throughout the gastrointestinal tract. The accumulation of mutations in these stem cells is the likely cause of most gastrointestinal cancers. Clonal analysis of these stem cell populations has revealed how normal homeostatic processes work and how neoplastic growth occurs. In this review, we consider the clonal dynamics of stem cells in the gastrointestinal tract. We focus on mechanisms of clonal expansion, and discuss the novel methods that have been developed to study these processes in humans. Particular consideration is given to the role of clonal analysis in understanding dysplasia and neoplasia. We consider how improvements in sequencing technology may shape future research and clinical practice.

This article focuses on preventing the initiation and promotion of neoplastic growth in colon cancer, particularly with dietary measures. A goal of dietary epidemiology is to identify chemopreventive agents and strategies. The effects of diet are analyzed by observational approaches and experimental dietary, nutritional, or chemopreventive interventions. Short-term trials that alter intermediate biomarkers that are more sensitive than the adenoma to interventions may be necessary. The same logic needs to be applied to chemoprevention. Nonsteroidal anti-inflammatory drugs, calcium, and selenium have some individual effects that could be potentiated if added together. The current evidence is that the combined effect of all three agents is modest, compared with the effects of screening, or even those of smoking cessation.

In the past 30 years we have witnessed an extraordinary progress on the research in the molecular biology of cancer, but its medical treatment, widely based on empirically established protocols, still has many limitations. One of the reasons for that is the limited quantitative understanding of the dynamics of tumor growth and drug response in the organism. In this review we shall discuss in general terms the use of mathematical modeling and computer simulations related to cancer growth and its applications to improve tumor therapy. Particular emphasis is devoted to multiscale models which permit integration of the rapidly expanding knowledge concerning the molecular basis of cancer and the complex, nonlinear interactions among tumor cells and their microenvironment that will determine the neoplastic growth at the tissue level.

Background and Aims The biological environment varies across the colorectum and may therefore affect neoplastic growth differently in the proximal and distal colon. The aim of the study was to evaluate the risk for recurrent adenomas and their anatomic location based on adenoma location at baseline colonoscopy. Methods Data were extracted from 3 adenoma prevention trials (n = 2430). Participants had at least 1 adenoma at baseline colonoscopy and underwent subsequent surveillance colonoscopy, at which time metachronous adenomas could be detected. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for metachronous adenomas by location of the baseline lesion and considered the impact of advanced neoplasia and multiplicity. Results At baseline, 522 patients (21.5%) had adenomas only in the proximal colon, 1266 patients (52.1%) had adenomas only in the distal colorectum, and 642 (26.4%) had adenomas in both regions. Overall, 877 patients (36.5%) had metachronous adenomas during the follow-up period. Those with only proximal adenomas at baseline had a higher risk of metachronous adenomas compared with patients with only distal adenomas (RR, 1.17; 95% CI, 1.01–1.35). A greater proximal risk was found after restricting the analysis to patients with multiple proximal adenomas versus multiple distal adenomas (RR, 1.35; 95% CI, 1.10–1.67). The risk of recurrent adenomas on the same side was 48% higher for patients with only proximal adenomas at baseline compared with those with only distal adenomas at baseline (RR, 1.48; 95% CI, 1.22–1.80). Conclusions Patients with proximal adenomas only have a modestly greater risk of adenoma recurrence than patients with adenomas limited to the distal colon, and have a greater likelihood of adenoma recurrence on the same side compared with patients with distal adenomas. This observation suggests that biological factors may differentially affect neoplasia growth across the colon.

Cancer poses danger because of its unregulated growth, development of resistant subclones, and metastatic spread to vital organs. Although the major transitions in cancer development are increasingly well understood, we lack quantitative theory for how preventive measures and post-excision ('reactive') treatments are predicted to affect risks of obtaining a life threatening cancer or relapse, respectively. We employ analytical and numerical models to evaluate how continuous measures such as life style changes, and certain non-targeted and targeted treatments affect both neoplastic growth and the frequency of resistant clones. We find that preventive measures can have a negligible impact on pre-cancerous lesions and yet achieve considerable reductions in risk of invasive cancer. Importantly, our model, based on realistic parameter estimates, predicts that daily cancer cell arrest levels of 0.2-0.3% produce optimal outcomes for prevention, whereas for reaction the level is 0.3-0.4%. For similar cancer cell populations, prevention outcomes are, on average, always better than reactive ones. This is because reactive measures are more likely to select for faster growing subclones with higher probabilities of resistance, highlighting the difficulty in countering relapse regardless of therapeutic impact on cancer cell populations. We discuss these results and other important mitigating factors that need to be taken into consideration in a comparative understanding of preventive versus reactive treatments.

Since angiogenesis plays an important role in cancer growth, infiltration and metastasis, many agents targeting this pathway have been developed over the last decade. Antiangiogenic drugs interfere with this process and may inhibit neoplastic growth or induce tumor dormancy by blocking the expanding network of newly formed capillaries. Despite the initial promise, targeting angiogenesis in breast cancer has not reached major breakthroughs. Nevertheless, the immunologic role of VEGF deserves to be further explored. We aim to describe the biological mechanisms which underlie the role of angiogenesis in breast cancer carcinogenesis, to depict its contribution to the metastatic process and to review the most important clinical trials testing angiogenic inhibitors in breast cancer, including monoclonal antibodies and novel small molecules.

For most organisms oxygen is essential for life. When oxygen levels drop below those required to maintain the minimum physiological oxygen requirement of an organism or tissue it is termed hypoxia. To counteract possible deleterious effects of such a state, an immediate molecular response is initiated causing adaptation responses aimed at cell survival. This response is mediated by the hypoxia-inducible factor-1 (HIF-1), which is a heterodimer consisting of an α- and a β-subunit. HIF-1α protein is stabilized under hypoxic conditions and therefore confers selectivity to this response. Hypoxia is characteristic of tumors, mainly because of impaired blood supply resulting from abnormal growth. Over the past few years enormous progress has been made in the attempt to understand how the activation of the physiological response to hypoxia influences neoplastic growth. In this review some aspects of HIF-1 pathway activation in tumors and the consequences for pathophysiology and treatment of neoplasia are discussed.

Phosphatase and tensin homolog (Pten) suppresses neoplastic growth by negatively regulating PI(3)K signaling through its phosphatase activity.1 Indeed, most missense mutations detected in human tum...

Neoplastic growth occurs from the very beginning to the end of the human life span, with a predominant age span for the clinical incidence of each cancer. Most cancers are diagnosed during the second half of human life span, but their natural histories start much earlier than their clinical manifestations. The clinical incidence declines after ages 75–80 years. The histology, the evolution, and the distribution of the frequency of the different cancers during the human life span suggest that neoplastic growth is a dynamic process where new variables are continuously created, the result of the interaction of individual genetics, environmental aggressions, and the developmental stages of the human life span. Data suggest that in many instances tumor growth can be looked upon as a deviation from normal development. Mechanisms are described that can explain the decline of the incidence and the progression during senescence in terms of the changes occurring in the human organism during the last developmental stages.

The basic concept of immunotherapy in cancer is to enable the immune system to detect neoplastic growth and to either prevent carcinogenesis and/or reject transformed cells with a potential for malignant tumor growth. Taking into account the enormous success of vaccines against infectious diseases, such an approach has the potential of not only successfully treating cancer patients but also preventing recurrences for an extended period of time.

Chronic osteomyelitis usually present as bony growth but it can rarely present as a soft tissue growth mimicking neoplasm and is usually diagnosed by the combination of radiology and microbiology. This is a case report of an adult male who had chronic osteomyelitis mimicking a neoplastic growth of soft tissue. CT scan showed soft tissue mass mimicking a soft tissue tumor but microbiology test and MRI confirmed the diagnosis of chronic osteomyelitis.

Neoplastic transformation is a consequence of maladaptive alterations in the cellular processes normally involved in cell growth, proliferation, differentiation, and survival. Despite the relative infrequent nature of skeletal neoplasms, current understanding of the pathobiology underlying these conditions is becoming increasingly characterized. This article highlights some of the established molecular abnormalities identified in various benign and malignant skeletal neoplasms and how they pertain to tumor biology, diagnosis, and prognosis. Most of the commonly accepted cellular aberrancies in skeletal neoplasms pertain to mutations, copy number changes, and/or chromosomal rearrangements. However, it is becoming increasingly understood that the complexity of tumorigenic pathways necessary for neoplastic growth are manipulated by numerous overlapping alterations in the genetic code and are further influenced by higher-order molecular programs, such as pretranscriptional and posttranscriptional regulation and chromatin reorganization. Over time, identification and quantification of these increasingly recognized neoplastic processes will gradually translate into valuable clinical applications, enhancing the current diagnostic and prognostic capabilities.

How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.

Fast and non-invasive, diagnostic techniques based on fluorescence spectroscopy have the potential to link the biochemical and morphologic properties of tissues to individual patient care. One of the most widely explored applications of fluorescence spectroscopy is the detection of endoscopically invisible, early neoplastic growth in epithelial tissue sites. Currently, there are no effective diagnostic techniques for these early tissue transformations. If fluorescence spectroscopy can be applied successfully as a diagnostic technique in this clinical context, it may increase the potential for curative treatment, and thus, reduce complications and health care costs. Steady-state, fluorescence measurements from small tissue regions as well as relatively large tissue fields have been performed. To a much lesser extent, time-resolved, fluorescence measurements have also been explored for tissue characterization. Furthermore, sources of both intrinsic (endogenous fluorophores) and extrinsic fluorescence (exogenous fluorophores) have been considered. The goal of the current report is to provide a comprehensive review on steady-state and time-resolved, fluorescence measurements of neoplastic and non-neoplastic, biologic systems of varying degrees of complexity. First, the principles and methodology of fluorescence spectroscopy are discussed. Next, the endogenous fluorescence properties of cells, frozen tissue sections and excised and intact bulk tissues are presented; fluorescence measurements from both animal and human tissue models are discussed. This is concluded with future perspectives.

Background and Objectives It is possible to formulate models capable of reproducing the main details of the physical processes involved in the evolution of biological systems. The complexity of the problem requires to begin with a simple and universal model for the description of the cellular growth, to be adapted successively to the local conditions found in clinically observed neoplastic growths. Methods A model based on the Local Interaction Simulation Approach (LISA) has been formulated for the simulation of growth, diffusion, and metastasis of neoplasms. The vascularization is described by a blood vessel located on one edge of the specimen in which a constant and homogeneous flow is assumed. A nutrient density is defined to mimic the blood flow within the tissue. Results Photograms taken at proper times may identify the main characteristics of the tumor evolution and describe its volume variations in a transversal section. Furthermore, it is possible to monitor constantly the volume of the neoplasm and of the necrotic tissue as a function of time, as well as the portion of cells that have migrated in the blood vessel. Conclusions In spite of strong simplifying assumptions, the model presents good qualitative agreement with clinical data, which may be further improved by more detailed information about cancer cells properties or local vascular system patterns. J. Surg. Oncol. 2000;74:122–129. © 2000 Wiley-Liss, Inc.

Polycystic kidney disease (PKD) has a number of characteristics that make it uniquely challenging for the development of therapies to slow disease progression. Renal cystic diseases result from the neoplastic growth of numerous fluid-filled cysts, often accompanied by increased apoptosis, tissue

Amphibian tissues seem to resist oncogenesis in proportion to their regenerative capacity, a phenomenon most easily seen in relation to limb regeneration. There is evidence that mammalian tissues also possess, in addition to and distinct from the capacity for physiological renewal, a limited and not always overtly evident degree of amphibian-like capacity for regeneration (epimorphic regeneration). It is the thesis of this paper that cancer in mammals would seldom occur were it not for a local destruction or exhaustion, secondary to injury or aging, of this normal amphibian-like regenerative capacity.

Many patients with cancer are afflicted with an array of severe ailments caused by remote effects of the neoplasm on distant organs, which it has not invaded or colonized. The growing local tumor dominates attention, but invisible chemical and cellular components released by this parasitic neoplastic growth can operate below the threshold of detection to derange feedback loops coordinating essential physiological functions. Ultimately, these changes cause serious signs and symptoms, collectively described as paraneoplastic syndromes (PNSs), which significantly diminish the patient’s quality of life. PNS can appear before, or after, detection of the cancer and are sometimes surprising or even bizarre. The patterns of clinical changes seen in these patients are caused by a range of mechanisms that reveal intricate networks of communications between different body systems, normally utilized for healthy function. For example, these disorders demonstrate that (1) hormones, peptides, and other long- and short-range signaling molecules produced by the tumor and (2) immune reactions to tumor-related antigens, can mediate diverse destabilizing effects. However, comparative analysis of numerous PNS reveals valuable information indicating that the primary pathogenetic events instigating these disturbances are much more fundamental. This article provides an overview of the diverse clinical manifestations of paraneoplastic disorders, with representative examples and presents evidence that inappropriate gene expression in the tumor, caused by loss of regulatory control, is a novel unifying explanation for such wide effects of the neoplasm on the host. It also discusses treatment options and issues relating to conducting randomized clinical trials on these disorders.

Inactivation of Drosophila tumor suppressor genes can cause excessive proliferation and, in some cases, neoplastic growth. Neoplastic growth in Drosophila tissues can also be followed by metastasis upon transplantation into hosts or in vivo. Recently, we have shown that metastatic tumors of Drosophila can provide a model in which to identify genes that are involved in the metastatic process.

From the study of standard textbooks of dermatology, no comprehensive understanding of the word nevus can be derived. The purpose of this article is to formulate a workable definition. As a first step, various definitions proposed by previous authors are reviewed. Their inconsistency appears to be mainly due to the fact that the term nevus is used to denote both neoplastic and nonneoplastic, congenital and acquired as well as hereditary and nonhereditary skin lesions. Taking this difficulty into account, the author suggests, as a unifying concept, the new category of genetic mosaicism. The following definition is proposed: 'Nevi are visible, circumscribed, long-lasting lesions of the skin or the neighboring mucosa, reflecting genetic mosaicism. With the exception of melanocytic nevi, they do not show neoplastic growth. They never show malignant neoplasia.'--For several types of nevi the concept of genetic mosaicism has already been confirmed at the cellular level. Future cytogenetic and molecular studies should show whether the proposed definition is valid for all other types of nevi and thus generally acceptable.

Genomic instability is a hallmark of colorectal cancer. Progressive accumulation of mutations leads to deregulation of cellular events, acquired growth advantage, and clonal expansion of abnormal cells. Subsequently, these cells become more susceptible to mutations increasing the likelihood of critical mutations and giving rise to histopathologically identifiable neoplastic growth and metastatic behavior.

Since the microbiological revolution, most infectious diseases have been defined and classified according to an etiologic criterion, i.e. the identification of single, external "necessary" causes (for example, Mycobacterium for tuberculosis). This is not the case with cancer. Not only external "necessary" causes of cancer have not been identified, but also the morphological classification cannot be based on univocal criteria. Although "neoplasia" and "anaplasia" appear to be universal attributes of cancer, these events are only quantitative. Neoplastic growth can be fast or slow (development may take weeks or years), and tissue pathologies are difficult to detect from normal tissue in some cancers but are obvious in others. Common special properties of anaplasia appear to be concealed in the wide range of morphologies. In the absence of a coherent morphological definition, and of external necessary causes (such as bacteria for infectious diseases), a mechanistic definition could be adopted. However, unless molecular biology discovers specific mechanistic steps in carcinogenesis, which indicate the existence of "necessary" events in carcinogenesis, we cannot adopt a univocal (monothetic) definition of cancer. The alternative is to use a polythetic definition, according to Wittgenstein's model of a "long rope twisted together out of many shorter fibres."

We report a case of an 83-year-old previously healthy female patient presenting with a swiftly evolving erythematous violaceous, infiltrative, ulcerated onion like mass with hyperkeratotic surface on the left ear lobe. The lesion was excised and resulted as an atypical fibroxanthoma, an extremely rare neoplastic growth, being a superficial variant of pleomorphic malignant fibrous histiocytoma. A brief review of dia-gnosis, treatment and prognosis is discussed.

The cell is a complex system functioning outside a thermodynamic equilibrium. The prediction of cellular functions based exclusively on molecular evidence is still impossible because of the large number of interacting molecules and the nonlinear interactions between cellular subsystems. The system cell displays a surprisingly small spectrum of macroscopically observable degrees of freedom. Their number and characteristics, however, are different in normal and neoplastic growth. As illustrated by image analytical, microanalytical and other cell biological data we demonstrate that certain cellular observables--termed order parameters--may serve as indicators for normal and neoplastic growth. The data indicate that the transition between normal and neoplastic growth can be understood as a phase transition of the mitogenic signalling network. In this interpretation, the order parameters of normal and neoplastic cells are the result of cellular self-organization.

Angiogenesis is an essential step for breast cancer progression and dissemination. The development of new blood vessels in cancer setting (angiogenesis) is conducted by numerous physiological and pathological stimuli, where the main stimulus is hypoxia. The knowledge of different molecular pathways regulating angiogenesis is constantly growing. An increased and complex scenario of angiogenesis is nowadays available in breast cancer, specifically, and permits not only to understand most of the important phases of neoplastic growth but also offer an exciting perspective for new therapeutic proposals based on blocking new blood vessels sprouting. This review focused on historical and recent understanding of angiogenesis occurrence in breast cancer.

SummaryParenterally-administered 2,4-D produces temporary myotonia in mice, rats, rabbits and dogs following a single injection. Repeated injections have failed to elicit either a characteristic chronic syndrome or a striking histologic picture; nor have they altered the process of reproduction and development in the dose ranges tested. The slight retardation of the growth rate of young mice on large daily doses is probably a manifestation of reduced food intake. Neoplastic growth has not been inhibited.The author is grateful to Dr. Joseph C. Aub for the suggestion of this problem and for encouragement and advice. The technical help of Amory Glenn is also greatly appreciated.